Insights from structures of cancer-relevant pre-mRNA splicing factors.

Abstract

Pre-mRNA splicing factors recognize consensus signals within preliminary transcripts, and as cogs of the spliceosome machine, orchestrate the excision and rejoining of pre-mRNA regions for gene expression. Large-scale sequencing has demonstrated that mutations in key genes encoding pre-mRNA splicing factors are common among myeloid neoplasms and also occur in a variety of other cancers. This revelation offers new therapeutic opportunities to target pre-mRNA splicing vulnerabilities in hematologic and other malignancies. The mutated residues typically alter 3' splice site choice for a subset of transcripts. In this review, we highlight mechanistic insights from recent 3D structures that reveal the affected residues poised for pre-mRNA recognition.

• Authors: Clara L Kielkopf
• Journal: Current opinion in genetics & development (Curr Opin Genet Dev) Vol. 48 Pg. 57-66 (02 2018) ISSN: 1879-0380 [Electronic] England
• PMID: 29128695 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• RNA Splicing Factors

Topics

• Animals
• Humans
• Mutation
• Neoplasms (metabolism)
• RNA Splicing Factors (chemistry, genetics, metabolism)
• Spliceosomes (chemistry, metabolism)