Since its original identification as a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex, K protein has been found not only in the nucleus but also in the cytoplasm and mitochondria and is implicated in chromatin remodeling, transcription, splicing and translation processes. K protein contains multiple modules that, on one hand, bind kinases while, on the other hand, recruit chromatin, transcription, splicing and translation factors. Moreover, the K‐ protein‐mediated interactions are regulated by signaling cascades. These observations are consistent with K (...) protein acting as a docking platform to integrate signaling cascades by facilitating cross‐talk between kinases and factors that mediate nucleic‐acid‐directed processes. Comparison of K across species reveals that it is an essential factor in metazoans, but not in yeast. Although some of the K protein interactions and functions are conserved in eukaryotes from yeast to man, the mammalian protein seems to play a wider role. The greater diversity of mammalian K protein interactions and function may reflect gain of novel docking sites and expansion evolutionary of gene expression networks. BioEssays 26:629–638, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This article describes the discovery of nuclear DNA‐like RNA (dRNA or hnRNA) and ribonucleoprotein particles in eukaryotes. Native hnRNA particles were isolated by sucrose gradient sedimentation and their structural organisation – nucleic acid (i.e. RNA) wrapped in a regular way on the surface of a series of globular protein particles – was determined. This led to the formulation of the informofer cycle hypothesis for the synthesis of hnRNA as a giant precursor molecule, its transport in informosomes within the nucleus, and (...) subsequent splicing before export from the nucleus as free mRNA. (shrink)

In eukaryotic cells, messenger RNAs are formed by extensive posttranscriptional processing of primary transcripts, assembled with a large number of proteins and processing factors in ribonucleoprotein complexes. The protein moiety of these complexes mainly constitutes a class of about 20 major polypeptides called heterogeneous nuclear ribonucleoproteins or hnRNPs. The function and the mechanism of action of hnRNPs is still not fully understood, but the identification of RNA binding domains and RNA binding specificities, and the development of new functional (...) assays, has stimulated interest in them. In contrast to previous models that hypothesised a mere structural (histone‐like) function, a more diversified and dynamic role for these proteins is now emerging. In fact, they can be viewed as a subset of the trans‐acting pre‐mRNA maturation factors. They might actively participate in post‐transcriptional events such as regulated splicing and mRNA export. Moreover, recent data suggest an involvement of some of these proteins in molecular diseases. Here we present an overview of the most relevant properties of hnRNPs and discuss some emerging ideas on theiir roles. (shrink)

Recent experimental evidence suggests that most of the genome is transcribed into non‐coding RNAs. The initial transcripts undergo further processing generating shorter, metabolically stable RNAs with diverse functions. Small nucleolar RNAs (snoRNAs) are non‐coding RNAs that modify rRNAs, tRNAs, and snRNAs that were considered stable. We review evidence that snoRNAs undergo further processing. High‐throughput sequencing and RNase protection experiments showed widespread expression of snoRNA fragments, known as snoRNA‐derived RNAs (sdRNAs). Some sdRNAs resemble miRNAs, these can associate with argonaute proteins and (...) influence translation. Other sdRNAs are longer, form complexes with hnRNPs and influence gene expression. C/D box snoRNA fragmentation patterns are conserved across multiple cell types, suggesting a processing event, rather than degradation. The loss of expression from genetic loci that generate canonical snoRNAs and processed snoRNAs results in diseases, such as Prader‐Willi Syndrome, indicating possible physiological roles for processed snoRNAs. We propose that processed snoRNAs acquire new roles in gene expression and represent a new class of regulatory RNAs distinct from canonical snoRNAs.Also watch the Video Abstract. (shrink)

Recent findings indicate that substantial cross‐talk may exist between transcriptional and post‐transcriptional processes. Firstly, there are suggestions that specific promoters influence the post‐transcriptional fate of transcripts, pointing to communication between protein complexes assembled on DNA and nascent pre‐mRNA. Secondly, an increasing number of proteins appear to be multifunctional, participating in transcriptional and post‐transcriptional events. The classic example is TFIIIA, required for both the transcription of 5S rRNA genes and the packaging of 5S rRNA. TFIIIA is now joined by the Y‐box (...) proteins, which bind DNA (transcription activation and repression) and RNA (mRNA packaging). Furthermore, the tumour suppressor WT1, at first thought to be a typical transcription factor, may also be involved in splicing; conversely, hnRNP K, a bona fide pre‐mRNA‐binding protein, appears to be a transcription factor. Other examples of multifunctional proteins are mentioned: notably PTB, Sxl, La and PU.1. It is now reasonable to assert that some proteins, which were first identified as transcription factors, could just as easily have been identified as splicing factors, hnRNP, mRNP proteins and vice versa. It is no longer appropriate to view gene expression as a series of compartmentalised processes; instead, multifunctional proteins are likely to co‐ordinate different steps of gene expression. (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 noncoding RNA 7SK is a critical regulator of transcription by adjusting the activity of the kinase complex P‐TEFb. Release of P‐TEFb from 7SK stimulates transcription at many genes by promoting productive elongation. Conversely, P‐TEFb sequestration by 7SK inhibits transcription. Recent studies have shown that 7SK functions are particularly important for neuron development and maintenance and it can thus be hypothesized that 7SK is at the center of many signaling pathways contributing to neuron function. 7SK activates neuronal gene expression programs (...) that are key for terminal differentiation of neurons. Proteomics studies revealed a complex protein interactome of 7SK that includes several RNA‐binding proteins. Some of these novel 7SK subcomplexes exert non‐canonical cytosolic functions in neurons by regulating axonal mRNA transport and fine‐tuning spliceosome production in response to transcription alterations. Thus, a picture emerges according to which 7SK acts as a multi‐functional RNA scaffold that is integral for neuron homeostasis. (shrink)