Splicing regulation: from a parts list of regulatory elements to an integrated splicing code.
Alternative splicing of pre-mRNAs is a major contributor to both proteomic diversity and control of gene expression levels. Splicing is tightly regulated in different tissues and developmental stages, and its disruption can lead to a wide range of human diseases. An important long-term goal in the splicing field is to determine a set of rules or "code" for splicing that will enable prediction of the splicing pattern of any primary transcript from its sequence. Outside of the core splice site motifs, the bulk of the information required for splicing is thought to be contained in exonic and intronic cis-regulatory elements that function by recruitment of sequence-specific RNA-binding protein factors that either activate or repress the use of adjacent splice sites. Here, we summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions.
Wang
Zefeng
Z
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. zefeng@med.unc.edu
Burge
Christopher B
CB
D017398:Alternative Splicing; D000818:Animals; D004742:Enhancer Elements, Genetic; D005091:Exons; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing; D037941:Silencer Elements, Transcriptional
D012322:RNA Precursors