# Exploring Disordered Regions of Human Spliceosome Proteins

## TL;DR

This paper explores disordered regions in human spliceosome proteins, showing they are common, evolutionarily conserved, and linked to cancer.

## Contribution

The study provides a comprehensive analysis of disordered regions in the human spliceosome and their roles in regulation and disease.

## Key findings

- Many spliceosome proteins contain over 40% disordered residues.
- Disorder is driven by compositional bias and is evolutionarily conserved.
- IDRs are hotspots for cancer mutations and post-translational modifications like phosphorylation.

## Abstract

Introns
are removed from mRNAs by the spliceosome, a
type of protein–RNA
machinery enriched with intrinsically disordered regions (IDRs). Lacking
stable 3D structures, IDRs can adopt diverse conformations interlacing
protein and RNA components of the spliceosome and regulating splicing.
In this work, we performed a comprehensive bioinformatics analysis
of the human spliceosome proteome, revealing that many proteins contain
more than 40% disordered residues. Spliceosome IDRs are mainly driven
by compositional bias due to an excess of charged and RS-like sequences,
with 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 hot spots for cancer-associated
mutations, which have been implicated in different types of cancer.
Our results collectively underscore the central role of IDRs in splicing
regulation and disease.