Pre-mRNA splicing: where and when in the nucleus

Abstract

Alternative splicing is a process to differentially link exon regions in a single precursor mRNA to produce two or more different mature mRNAs, a strategy frequently used by higher eukaryotic cells to increase proteome diversity and/or enable additional post-transcriptional control of gene expression. This process can take place either co-transcriptionally or post-transcriptionally. When and where RNA splicing takes place in the cell represents a central question of cell biology; co-transcriptional splicing allows functional integration of transcription and RNA processing machineries, and could allow them to modulate one another, whereas post-transcriptional splicing could facilitate coupling RNA splicing with downstream events such as RNA export to create additional layers for regulated gene expression. This review focuses on recent advances in co- and post-transcriptional RNA splicing and proposes a new paradigm that some specific coupling events contribute to genome organization in higher eukaryotic cells.

Frac-seq reveals isoform-specific recruitment to polyribosomes

“…It is clear that the trans-acting factors associated with alternative mRNA isoforms can vary just as distinctly as the protein-coding capacities of the messages they encode. Many RNA binding proteins, including shuttling proteins, are implicated in multiple steps of posttranscriptional gene regulation, including mRNA export, stability, surveillance, localization, and translation (Sanford and Caceres 2004;Zhang and Krainer 2004;Zhong et al 2009;Han et al 2011). These factors can be transcript-associated throughout the life cycle of an mRNA and may coordinate nuclear and cytoplasmic steps of gene expression (Dreyfuss et al 2002;Nashchekin et al 2007;Kylberg et al 2008).…”

Aberrantly splicedHTT,a new player in Huntington’s disease pathogenesis

“…Additionally, transcription of longer intronic sequences not only allows for increased spatial, but also increased temporal regulation of splicing. While splicing is thought to usually occur co-transcriptionally, 35 the extreme length of HTT intron 1 could open up a kinetic window for additional factors to act on transcription, splicing, and/or cryptic polyadenylation site activation. In addition, the rare splice site sequence discussed earlier might result in a reduction in the kinetics of U1 small nuclear ribonucleoprotein complex recruitment or the higher instability of spliceosomes.…”

Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles

“…Several lines of evidence suggest that nuclear speckles function as storage, assembly, and modification compartments, which supply splicing and transcription factors to active transcription sites (Lamond and Spector 2003). Other findings have described a model in which nuclear speckles act as hubs that facilitate efficient integration of distinct steps during gene expression, from transcription to mRNA export (Hall et al 2006;Han et al 2011). The function of nuclear speckles is still debatable; therefore, analysis of the structural and functional components of nuclear speckles is an important step toward improving our understanding of nuclear speckle functions.…”