Eukaryotic gene expression is extensively controlled at the level of mRNA stability and the mechanisms underlying this regulation are markedly different from their archaeal and bacterial counterparts. We propose that two such mechanisms, nonsense‐mediated decay (NMD) and motif‐specific transcript destabilization by CCCH‐type zinc finger RNA‐binding proteins, originated as a part of cellular defense against RNA pathogens. These branches of the mRNA turnover pathway might have been used by primeval eukaryotes alongside RNA interference to distinguish their own messages (...) from those of RNA viruses and retrotransposable elements. We further hypothesize that the subsequent advent of “professional” innate and adaptive immunity systems allowed NMD and the motif‐triggered mechanisms to be efficiently repurposed for regulation of endogenous cellular transcripts. This scenario explains the rapid emergence of archetypical mRNA destabilization pathways in eukaryotes and argues that other aspects of post‐transcriptional gene regulation in this lineage might have been derived through a similar exaptation route. -/- . (shrink)

Degradation of eukaryotic RNAs that contain premature termination codons (PTC) during nonsense‐mediated mRNA decay (NMD) is initiated by RNA decapping or endonucleolytic cleavage driven by conserved factors. Models for NMD mechanisms, including recognition of PTCs or the timing and role of protein phosphorylation for RNA degradation are challenged by new results. For example, the depletion of the SMG5/7 heterodimer, thought to activate RNA degradation by decapping, leads to a phenotype showing a defect of endonucleolytic activity of NMD complexes. (...) This phenotype is not correlated to a decreased binding of the endonuclease SMG6 with the core NMD factor UPF1, suggesting that it is the result of an imbalance between active (e.g., in polysomes) and inactive (e.g., in RNA‐protein condensates) states of NMD complexes. Such imbalance between multiple complexes is not restricted to NMD and should be taken into account when establishing causal links between gene function perturbation and observed phenotypes. (shrink)

Gene expression is an inherently complex process and errors often occur during the transcription and processing of mRNAs. Several surveillance mechanisms have evolved to check the fidelity at each step of mRNA manufacture. Two recent reports describe the identification of a novel pathway in eukaryotes that recognizes and degrades mRNAs that lack a stop codon.1,2 The non‐stop decay mechanism releases ribosomes stalled at the 3′ end of a mRNA and stimulates the exosome to rapidly degrade the transcript. (...) BioEssays 24:785–788, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Genotoxic stress leads to DNA damage which can be detrimental to the cell. A well‐orchestrated cellular response is mounted to manage and repair the genotoxic stress‐induced DNA damage. Our understanding of genotoxic stress response is derived mainly from studies focused on transcription, mRNA splicing, and protein turnover. Surprisingly not as much is understood about the role of mRNA translation and decay in genotoxic stress response. This is despite the fact that regulation of gene expression at the level (...) of mRNA translation and decay plays a critical role in a myriad of cellular processes. This review aims to summarize some of the known findings of the role of mRNA translation and decay by focusing on two categories of examples. We discuss examples of mRNA whose fates are regulated in the cytoplasm and RNA‐binding proteins that regulate mRNA fates in response to genotoxic stress. (shrink)

The expression of protein‐encoding genes is a complex process culminating in the production of mature mRNA and its translation by the ribosomes. The production of a mature mRNA involves an intricate series of processing steps. The majority of eukaryotic protein‐encoding genes contain intron sequences that disrupt the protein‐encoding frame, and hence have to be removed from immature mRNA prior to translation into protein. The mechanism involved in the selection of correct splice sites is incompletely understood. A considerable (...) body of evidence suggests that the splicing machinery has suboptimal efficiency and fidelity leading to substantial processing inaccuracy. Here we discuss a recently published article1 that extends observations that cells rely on nonsense‐mediated mRNA decay (NMD) to compensate for such suboptimal processing accuracy. Intriguingly these authors provide evidence for a strong selective pressure in favour of premature termination of mRNA translation in the event of intron retention. The analysis presented implies a positive role of NMD in transcript diversification through alternative splicing and suggest that this ancient surveillance mechanism may have co‐evolved with intron acquisition born from the need for quality control of splicing patterns. BioEssays 30:926–928, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Until recently, retention of introns in mature mRNAs has been regarded as a consequence of mis‐splicing. Intron‐retaining transcripts are thought to be non‐functional because they are readily degraded by nonsense‐mediated decay. However, recent advances in next‐generation sequencing technologies have enabled the detection of numerous transcripts that retain introns. As we review herein, intron‐retaining mRNAs play an essential conserved role in normal physiology and an emergent role in diverse diseases. Intron retention should no longer be overlooked as a key mechanism (...) that independently reduces gene expression in normal biology. Exploring its contribution to the development and/or maintenance of diseases is of increasing importance. (shrink)

Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels (...) in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. (shrink)

It has long been observed that human protein‐coding genes have a particular distribution of GC‐content: the 5′ end of these genes has high GC‐content while the 3′ end has low GC‐content. In 2012, it was proposed that this pattern of GC‐content could act as an mRNA identity feature that would lead to it being better recognized by the cellular machinery to promote its nuclear export. In contrast, junk RNA, which largely lacks this feature, would be retained in the nucleus (...) and targeted for decay. Now two recent papers have provided evidence that GC‐content does promote the nuclear export of many mRNAs in human cells. (shrink)

The explosion in sequencing technologies has provided us with an instrument to describe mammalian transcriptomes at unprecedented depths. This has revealed that alternative splicing is used extensively not only to generate protein diversity, but also as a means to regulate gene expression post‐transcriptionally. Intron retention (IR) is overwhelmingly perceived as an aberrant splicing event with little or no functional consequence. However, recent work has now shown that IR is used to regulate a specific differentiation event within the haematopoietic system by (...) coupling it to nonsense‐mediated mRNA decay (NMD). Here, we highlight how IR and, more broadly, alternative splicing coupled to NMD (AS‐NMD) can be used to regulate gene expression and how this is deregulated in disease. We suggest that the importance of AS‐NMD is not restricted to the haematopoietic system but that it plays a prominent role in other normal and aberrant biological settings. (shrink)

In a recent issue of Nature Communications Ukleja and co‐workers reported a cryo‐EM 3D reconstruction of the Ccr4‐Not complex from Schizosaccharomyces pombe with an immunolocalization of the different subunits. The newly gained architectural knowledge provides cues to apprehend the functional diversity of this major eukaryotic regulator. Indeed, in the cytoplasm alone, Ccr4‐Not regulates translational repression, decapping and deadenylation, and the Not module additionally plays a positive role in translation. The spatial distribution of the subunits within the structure is compatible with (...) a model proposing that the Ccr4‐Not complex interacts with the 5′ and 3′ ends of target mRNAs, allowing different functional modules of the complex to act at different stages of the translation process, possibly within a circular constellation of the mRNA. This work opens new avenues, and reveals important gaps in our understanding regarding structure and mode of function of the Ccr4‐Not complex that need to be addressed in the future. (shrink)

The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports (...) competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation. ADAR1 is also known to recruit proteins such as DROSHA to nascent transcripts. Still, many open questions remain. For instance, the biological role of the Z-DNA binding domains in ADAR1 is not defined. Moreover, the impact of ADAR1 on the RNA-folding landscape is unclear. In sum, moonlighting functions of ADAR1 may be manifold and have a great impact on the transcriptome. Adenosine to inosine RNA editing by ADAR1 is mostly known for its role in the innate immune response to help discriminate self from non-self RNA. Here we discuss the other face of ADAR1 that impacts on cellular processes independent of its editing function. These include Staufen-mediated-decay, mRNA processing, or miRNA maturation. (shrink)

Cells contain a myriad of membraneless ribonucleoprotein (RNP) condensates with distinct compositions of proteins and RNAs. RNP condensates participate in different cellular activities, including RNA storage, mRNA translation or decay, stress response, etc. RNP condensates are assembled via liquid‐liquid phase separation (LLPS) driven by multivalent interactions. Transition of RNP condensates into bodies with abnormal material properties, such as solid‐like amyloid structures, is associated with the pathogenesis of various diseases. In this review, we focus on how RNAs regulate multiple (...) aspects of RNP condensates, such as dynamic assembly and/or disassembly and biophysical properties. RNA properties – including concentration, sequence, length and structure – also determine the phase behaviors of RNP condensates. RNA is also involved in specifying autophagic degradation of RNP condensates. Unraveling the role of RNA in RNPs provides novel insights into pathological accumulation of RNPs in various diseases. This new understanding can potentially be harnessed to develop therapeutic strategies. (shrink)

Large protein assemblies are usually the effectors of major cellular processes. The intricate cell homeostasis network is divided into numerous interconnected pathways, each controlled by a set of protein machines. One of these master regulators is the CCR4‐NOT complex, which ultimately controls protein expression levels. This multisubunit complex assembles around a scaffold platform, which enables a wide variety of well‐studied functions from mRNA synthesis to transcript decay, as well as other tasks still being identified. Solving the structure of (...) the entire CCR4‐NOT complex will help to define the distribution of its functions. The recently published three‐dimensional reconstruction of the complex, in combination with the known crystal structures of some of the components, has begun to address this. Methodological improvements in structural biology, especially in cryoelectron microscopy, encourage further structural and protein‐protein interaction studies, which will advance our comprehension of the gene expression machinery. (shrink)

A myriad of coordinated signals control cellular differentiation. Reprogramming the cell's proteome drives global changes in cell morphology and function that define cell phenotype. A switch in alternative splicing of many pre‐mRNAs encoding neuronal‐specific proteins accompanies neuronal differentiation. Three groups recently showed that the global splicing repressor, polypyrimidine track‐binding protein (PTB), regulates this switch.1-3 Although a subset of neuronal genes are turned on in both non‐neuronal and neuronal cells, restricted expression of PTB in non‐neuronal cells diverts their mRNAs to nonsense‐mediated (...) decay and prevents protein expression. When the PTB brake is released, the cell splices like a neuron. BioEssays 30:1–4, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

When rates of transcription from specific genes change, delays of variable length intervene before the corresponding mRNAs and proteins attain new levels. For most mammalian genes, the time required to complete transcription, processing, and transport of mRNA is much shorter than the period needed to achieve a new, steady‐state level of protein. Studies of inducible genes have shown that the period required to attain new levels of individual mRNAs and proteins is related to their unique half‐lives. The basis for (...) this is a physical principle that predicts rates of accumulation of particles in compartmental systems. The minimum period required to achieve a new level is directly proportional to product half‐lives because rates of decay control the ratio between the rate of synthesis and the concentration of gene products at steady state. This kinetic model suggests that sensitivity of gene products to degradation by ribonucleases and proteinases is an important determinant of the time scale of gene expression. (shrink)

The multistep pathway of eukaryotic gene expression involves a series of highly regulated events in the nucleus and cytoplasm. In the nucleus, genes are transcribed into pre‐messenger RNAs which undergo a series of nuclear processing steps. Mature mRNAs are then transported to the cytoplasm, where they are translated into protein and degraded at a rate dictated by transcript‐ and cell‐type‐specific cues. Until recently, these individual nuclear and cytoplasmic events were thought to be primarily regulated by different RNA‐ and DNA‐binding proteins (...) that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that control both nuclear and cytoplasmic steps of gene expression. One such class of multifunctional proteins (e.g., Bicoid and Y‐box proteins) regulates both transcription and translation whereas another class (e.g., Sex‐lethal) regulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, spliceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytoplasmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway (nonsense‐mediated decay) that detects cytoplasmic signals (premature termination codons). We speculate that shuttling multifunctional proteins serve to efficiently link RNA metabolism in the cytoplasmic and nuclear compartments. BioEssays 23:775–787, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The genetic code is a set of instructions that determine how the information in our genetic material is translated into amino acids. In general, it is universal for all organisms, from viruses and bacteria to humans. However, in the last few decades, exceptions to this rule have been identified both in pro‐ and eukaryotes. In this review, we discuss the 16 described alternative eukaryotic nuclear genetic codes and observe theories of their appearance in evolution. We consider possible molecular mechanisms that (...) allow codon reassignment. Most reassignments in nuclear genetic codes are observed for stop codons. Moreover, in several organisms, stop codons can simultaneously encode amino acids and serve as termination signals. In this case, the meaning of the codon is determined by the additional factors besides the triplets. A comprehensive review of various non‐standard coding events in the nuclear genomes provides a new insight into the translation mechanism in eukaryotes. (shrink)

Renaissance logician, philosopher, humanist, and teacher, Peter Ramus (1515-72) is best known for his attack on Aristotelian logic, his radical pedagogical theories, and his new interpretation for the canon of rhetoric. His work, published in Latin and translated into many languages, has influenced the study of Renaissance literature, rhetoric, education, logic, and--more recently--media studies. Considered the most important work of Walter Ong's career, Ramus, Method, and the Decay of Dialogue is an elegant review of the history of Ramist scholarship (...) and Ramus's quarrels with Aristotle. A key influence on Marshall McLuhan, with whom Ong enjoys the status of honorary guru among technophiles, this challenging study remains the most detailed account of Ramus's method ever published. Out of print for more than a decade, this book--with a new foreword by Adrian Johns--is a canonical text for enthusiasts of media, Renaissance literature, and intellectual history. (shrink)

Neuronal signalling involves multiple neuropeptides that are diverse in structure and function. Complex patterns of tissue‐specific expression arise from alternate RNA splicing of neuropeptide‐encoding gene transcripts. The pattern of expression and its role in cell signalling is diffecult to study at the level of single neurons in the complex vertebrate brain. However, in the model molluscan system, Lymnaea, it is possible to show that alternate mRNA expression of the FMRFamide gene is specific to single identified neurons. Two different transcripts (...) are expressed in a mutually exclusive manner in different neurons. Post‐translational processing of the two precursor proteins leads to completely distinct sets of neuropeptide transmitters. The function of these transmitter cocktails, resulting from alternate mRNA splicing, was studied physiologically in identified neurons forming part of a behaviourally important network regulating heartbeat. (shrink)

Nuclear pre‐mRNAs must be precisely processed to give rise to mature cytoplasmic mRNAs. This maturation process, known as splicing, involves excision of intron sequences and ligation of the exon sequences. One of the major problems in understanding this process is how splice sites, the sequences which form the boundaries between introns and exons, can be accurately selected. A number of studies have defined conserved sequences within introns which were later shown to interact with small nuclear ribonucleoproteins (snRNPs). However, due to (...) the simplicity of these conserved sequences it has become clear that other elements must be involved and a number of studies have indicated the importance of secondary structures within pre‐mRNAs. Using various examples, we shall show that such structures can help to specify splice sites by modifying physical distances within introns or by being involved in the definition of exons and, lastly, that they can be part of the regulation of alternative splicing. (shrink)

Although the biological bases of forgetting remain obscure, the consensus among cognitive psychologists emphasizes interference processes, rejecting decay in accounting for memory loss. In contrast to this view, recent advances in understanding the neurobiology of long-term memory maintenance lead us to propose that a brain-wide well-regulated decay process, occurring mostly during sleep, systematically removes selected memories. Down-regulation of this decay process can increase the life expectancy of a memory and may eventually prevent its loss. Memory interference usually (...) occurs during certain active processing phases, such as encoding and retrieval, and will be stronger in brain areas with minimal sensory integration and less pattern separation. In areas with efficient pattern separation, such as the hippocampus, interference-driven forgetting will be minimal, and, consequently, decay will cause most forgetting. (shrink)

Six years ago, the Singer lab published a landmark paper which described how individual mRNA particles cross the nuclear pore complex in mammalian tissue culture cells. This involved the simultaneous imaging of mRNAs, each labeled by a large number of tethered fluorescent proteins and fluorescently tagged nuclear pore components. Now two groups have applied this technique to the budding yeast Saccharomyces cerevisiae. Their results indicate that in the course of nuclear export, mRNAs likely engage complexes that are present on (...) either side of the pore and that these interactions are modulated by proteins present in the messenger ribonucleoprotein (mRNP) complex. These findings lend support to the notion that just before and/or after the completion of nuclear export, mRNPs undergo one or more maturation steps that prepare the packaged mRNAs for translation. These results represent new and exciting insights into the mechanism of mRNA nuclear export. (shrink)

Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since (...) they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine has gained the attention of RNA biologists. The m6A modification has a set of writers, erasers, and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m6A epitranscriptome. The recent outburst of studies has brought the key role of mRNA N6-methyladenosine modification in post-transcriptional processing steps into the limelight. This review summarizes the current progress and the future prospective of m6A methylome. We addressed the debatable function of m6A modification and related modifiers in tumorigenesis and tumor progression. (shrink)

The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay pathway. Feng et al. now report a new function for UPF1—it is an E3 ubiquitin ligase that specifically promotes the decay of a key pro-muscle transcription factor: MYOD. UPF1 achieves this through its RING-like domain, which confers ubiquitin E3 ligase activity. Feng et al. provide evidence that the ability of UPF1 to destabilize MYOD represses myogenesis. In the future, it will be important (...) to define other protein substrates of UPF1-driven ubiquitination and to determine whether this biochemical activity is responsible for some of UPF1's previously defined biological functions, including in development and stress responses. The exciting findings presented by Feng et al. open up the possibility that protein turnover and RNA turnover are coupled processes. The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay pathway. Here we discuss a new role for UPF1—it is directly involved in protein decay. This hidden talent raises the possibility that protein turnover and RNA turnover are coupled processes. (shrink)

Corporate social responsibility (CSR) activities have become increasingly prevalent in retail settings. In franchised organizations, franchisors typically design and coordinate these activities, leaving operational execution to franchisees. Meanwhile, franchisors may introduce new corporate-led CSR activities over time. Even though changes to CSR activities may refocus outlets’ attention on a CSR initiative, they may also disrupt an outlet’s ongoing CSR routines. Using a longitudinal, secondary dataset consisting of an eight-year panel for a national, franchised restaurant chain, we examine CSR performance dynamics (...) in the presence of two distinct types of CSR activities: an ongoing CSR routine and a distinct, temporary CSR campaign. We find that, when resuming the CSR routine after a temporary CSR campaign, outlets’ performance in CSR routines drops significantly (i.e., immediate decay), then improves gradually (i.e., protracted recovery). We also consider the moderating role of an outlet’s experience, finding that experience stabilizes these decay and recovery cycles. Our findings represent a first step in developing a longitudinal understanding of how a firm’s short-term CSR campaigns may impact ongoing CSR routines, thus contributing to the knowledge of CSR activity development and routinization. (shrink)

The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay pathway. Feng et al. now report a new function for UPF1—it is an E3 ubiquitin ligase that specifically promotes the decay of a key pro-muscle transcription factor: MYOD. UPF1 achieves this through its RING-like domain, which confers ubiquitin E3 ligase activity. Feng et al. provide evidence that the ability of UPF1 to destabilize MYOD represses myogenesis. In the future, it will be important (...) to define other protein substrates of UPF1-driven ubiquitination and to determine whether this biochemical activity is responsible for some of UPF1's previously defined biological functions, including in development and stress responses. The exciting findings presented by Feng et al. open up the possibility that protein turnover and RNA turnover are coupled processes. The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay pathway. Here we discuss a new role for UPF1—it is directly involved in protein decay. This hidden talent raises the possibility that protein turnover and RNA turnover are coupled processes. (shrink)

Mary Astell (1666-1731) relies on a Cartesian account of the self to argue that both men and women are essentially thinking things and, hence, that both should perfect their minds or intellects. This account of the self might seem to ignore the inescapable fact that we have bodies. I argue that Astell accommodates the self’s embodiment along three dimensions. First, she tempers her sharp distinction between mind and body by insisting on their union. Second, she argues that the mind-body union (...) is good, at least when the body obeys the mind. Third, though Astell identifies the self with the mind, she identifies the person with the combination of mind and body. (shrink)

Climate change and the failure of crops are significant but overlooked events in the history of heredity. Bad weather and dangerously low harvests provided momentum and urgency for answers to questions about how best to improve and acclimatize staple varieties. In the 1790s, a series of crop failures in Britain led to the popularization of and widespread debate over Thomas Andrew Knight’s suggestion that poor weather was in fact largely unconnected to the bad harvests. Rather, Knight argued, Britain’s older varieties—particularly (...) its fruit trees—were coming to the natural end of their lifespans. At a period when Britain was trying to maximize its agricultural land usage, Knight campaigned that his fellow farmers ought to set aside land and resources in order to cultivate new varieties—an expensive and time-consuming procedure—in order to avoid disaster. In this paper, I argue that Knight’s lifelong commitment to his position demonstrates the role played by changes in climate and weather on popular understandings of plant heredity. Further, drawing upon the historiography of Britain’s climate and agriculture, I show that despite reliable weather and good harvests, Knight’s campaign survived for several decades before the continued health of Britain’s trees was finally treated as sufficient evidence to dispense with Knight’s warnings. This case provides a means of thinking about the history of heredity as it is shaped and impacted by changes in climate and local conditions. (shrink)

Despite a library full of literature on miRNA biology, core issues relating to miRNA target detection, biological effect, and mode of action remain controversial. This essay proposes that the predominant mechanism of direct miRNA action is translational inhibition, whereas the bulk of miRNA effects are mRNA based. It explores several issues confounding miRNA target detection, and discusses their impact on the dominance of “miRNA seed” dogma and the exploration of non‐canonical binding sites. Finally, it makes comparisons between miRNA target (...) prediction and transcription factor binding prediction, and questions the value of characterizing miRNA binding sites based on which miRNA nucleotides are paired with an mRNA. (shrink)

In Social Decay and Transformation social and political critic Samuel Farber presents an analysis of social decline that has been missing from the contemporary scene: a view from the Left, one which draws from the ideas and traditions of the Enlightenment's left wing. Using a comparative approach to situate his theoretical conclusions in historical circumstances, Farber looks at the working class and temperance movements, civil rights rebellions and the Black Panthers, and the cultural revolutions of 1920s Russia and the (...) Bolsheviks. Providing carefully reasoned interrogations of contemporary thinkers such as James C. Scott and Robin D. G. Kelley, Farber clarifies the discussions on social decay currently taking place, adding an important voice of the Left to the current debate. (shrink)

The expression of certain eukaryotic genes is – at least in part – controlled at the level of mRNA translation. The step of translational initiation represents the primary target for regulation. The regulation of the intracellular iron storage protein ferritin in response to iron levels provides a good example of translational control by a reversible RNA/protein interaction in the 5' untranslated region of an mRNA. We consider mechanisms by which mRNA/protein interactions may impede translation initiation and discuss (...) recent data suggesting that the ferritin example may represent the ‘tip of the iceberg’ of a more general theme for translational control. (shrink)

The authors discuss sonic decay as a compositional, performative and installation practice. Building off of the recording of a six hour performance, Andrew Stanford and Ezra Teboul assembled a short eight minute audio response which comes in two separate files. In addition to online links to the pieces, this paper provides a description of the compositional process along with an analysis of the response’s content and format. It then relates those to the greater concepts of sonic materialism, sound objects, (...) and the parallax view, and places the piece in the context of relevant and contemporary sound-based art works. Sonic Decay was installed and performed at the 2014 International Žižek Studies Conference in Cincinnati, Ohio. (shrink)

Dutch decline is usually studied as a topic in economic history: when did it really start, what shape did it take? In this article an attempt is made to show the actual awareness of the strengths and weaknesses of the Dutch economy, in the terms used by participants in three public debates. The classical Dutch discourse of decay and decline evolved in response to national and international political reality. The Bickerse Beroerten debate of 1650 shows the conflict between neo-Roman (...) and neo-Athenian tendencies. Subsequently, the explanation of Dutch decline (the effect of luxury) by the Anglo-Dutch pamphleteer Bernard Mandeville is shown to be markedly different from his advice to the English (to allow luxury). Finally, the 1630s Dutch debate between Lieven de Beaufort and his critics represents the maturing of the Dutch vocabulary of decline, including its failure to take into account the organisational preconditions of modern society. (shrink)

Why has the spread of fake news taken grip on society so quickly? Why has there been a significant increase in violence among those who disagree on issues? Why is it that increasingly our society is shutting down speech they disagree with rather than engage in civil debate? This book explores each of these issues and traces their connection to the same root cause: the decay of truth in education. It presents a compelling case that documents how educational institutions (...) and political institutions alike have abandoned truth as a primary virtue. In doing so, our society has waded deeply into an environment loaded with deceit, distraction, and delusion. The targets of this critique range across political, religious, and social groups as this is a societal-level outcome of the educational malaise towards truth. The book underscores topics of practical interest and considers real opportunities for each individual to take to help restore truth as a virtue in education and in society. (shrink)

Recent studies have shown that some maternal mRNAs are localized in specific cytoplasmic regions of eggs and embryos and are rearranged in concert with the cytoplasmic movements that fix the embryonic axes. The localization and ooplasmic segregation of mRNA molecules may be mediated by their association with specific egg cytoskeletal domains.

Considered the most important work of Walter Ong's career, Ramus, Method, and the Decay of Dialogue is an elegant review of the history of Ramist scholarship ...

The nomination of candidate genes underlying complex traits is often focused on genetic variations that alter mRNA abundance or result in non‐conservative changes in amino acids. Although inconspicuous in complex trait analysis, genetic variants that affect splicing or RNA editing can also generate proteomic diversity and impact genetic traits. Indeed, it is known that splicing and RNA editing modulate several traits in humans and model organisms. Using high‐throughput RNA sequencing (RNA‐seq) analysis, it is now possible to integrate the genetics (...) of transcript abundance, alternative splicing (AS) and editing with the analysis of complex traits. We recently demonstrated that both AS and mRNA editing are modulated by genetic and environmental factors, and potentially engender phenotypic diversity in a genetically segregating mouse population. Therefore, the analysis of splicing and RNA editing can expand not only the regulatory landscape of transcriptome and proteome complexity, but also the repertoire of candidate genes for complex traits. (shrink)

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work.This work is in the public domain in (...) the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work.As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant. (shrink)