Splicing of Pre ‐ m RNA

Abstract

Abstract Eukaryotic messenger ribonucleic acids (mRNAs) are initially transcribed as intron‐containing precursor mRNAs (pre‐mRNAs). Removal of introns from each pre‐mRNA by splicing occurs concurrently with ligation of the two flanking exons to generate a mature mRNA. Pre‐mRNA splicing is catalysed by the spliceosome, a large ribonucleoprotein complex containing five small nuclear RNAs and numerous protein factors. In higher eukaryotes, alternative splicing provides a mechanism to generate multiple mRNA isoforms from a single gene. Alternative splicing not only increases proteome diversity but also regulates the level of gene expression posttranscriptionally. Moreover, alternative splicing has a substantial impact on regulation of many physiological processes such as cell differentiation and development. Defects in pre‐mRNA splicing underlie a considerable number of genetic diseases and cancers. Key Concepts: In most eukaryotic pre‐mRNAs, the coding sequences (exons) are interrupted by stretches of noncoding sequences (introns). The spliceosome uses a two‐step transesterification reaction to remove introns and join exons of pre‐mRNAs. The snRNAs and spliceosomal protein Prp8 are implicated in the key catalytic steps of splicing. Alternative splicing extends proteome diversity and regulates gene expression levels. Alternative splicing is determined by interplays between trans ‐acting factors and cis ‐elements of pre‐mRNAs. Alteration of cis ‐elements and aberrant control of trans ‐acting factors lead to diseases.