The cellular internal ribosomal entry site (IRES) is one of the most important elements to mediate cap‐independent translational initiation, especially under conditions of stress and pathology. However, a high‐throughput method to discover IRESs in these conditions is still lacking. Here, a possible way IRES long‐read sequencing based on the latest high‐throughput technologies is proposed to solve this problem. Based on this design, diversity and integrity of the transcriptome from original samples can be kept. The micro‐environment that stimulates or inhibits IRES (...) activity can also be mimicked. By using long read‐length sequencing technology, additional experiments that are essential for ruling out the cryptic promoters or splicing events in routine IRES identification processes can be circumvented. It is hoped that this proposed methodology may be adopted for IRES element discovery, hence uncovering the full extent of the role of IRESs in disease, development, and stress. Also see the video abstract here https://youtu.be/JuWBbMzWXS8. (shrink)

Graphical AbstractCellular internal ribosomal entry site (IRES) is important for cap-independent translational initiation during stress and pathology. In article number 1900180, Lei-Yun Wang et al. propose an idea to discover IRES based on the latest high-throughput technologies, hence facilitating the understanding of IRES in disease development and treatment.