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Published on: June 30, 2022
Lives that introns lead after splicing
1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO, USA.
Abstract:
After transcription of a eukaryotic pre-mRNA, its introns are removed by the spliceosome, joining exons for translation. The intron products of splicing have long been considered 'junk' and destined only for destruction. But because they are large in size and under weak selection constraints, many introns have been evolutionarily repurposed to serve roles after splicing. Some spliced introns are precursors for further processing of other encoded RNAs such as small nucleolar RNAs, microRNAs, and long noncoding RNAs. Other intron products have long half-lives and can be exported to the cytoplasm, suggesting that they have roles in translation. Some viruses encode introns that accumulate after splicing and play important but mysterious roles in viral latency. Turnover of most lariat-introns is initiated by cleavage of their internal 2'-5' phosphodiester bonds by a unique debranching endonuclease, and the linear products are further degraded by exoribonucleases. However, several introns appear to evade this turnover pathway and the determinants of their stability are largely unknown. Whereas many stable intron products were discovered serendipitously, new experimental and computational tools will enable their direct identification and study. Finally, the origins and mechanisms of mobility of eukaryotic introns are mysterious, and mechanistic studies of the intron life cycle may yield new insights into how they arose and became widespread.
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