Exploring Disordered Regions of Human Spliceosome Proteins

Abstract

Introns are removed from messenger RNAs by the spliceosome, a protein-RNA machinery enriched with intrinsically disordered regions (IDRs). Lacking stable 3D structures, IDRs can adopt diverse conformations interlacing proteins and RNAs components of the spliceosome and regulating splicing. Here we performed a comprehensive bioinformatics analysis of the human spliceosome proteome revealing that many proteins contain over 40% of disordered residues. Spliceosome IDRs are mainly driven by compositional bias due to an excess of charged and RS-like sequences, with both the nature and extent of this disorder being broadly conserved evolutionarily. Additionally, these IDRs are frequent targets of post-translational modifications, especially phosphorylation, and are hotspots for cancer-associated mutations, implicated in different cancer types. Our results collectively underscore central role of IDRs in splicing regulation and disease. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/698225v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@a6ed0dorg.highwire.dtl.DTLVardef@11514b7org.highwire.dtl.DTLVardef@103387borg.highwire.dtl.DTLVardef@713fde_HPS_FORMAT_FIGEXP M_FIG C_FIG