Aberrant RNA Splicing in Cancer

RNA splicing, the enzymatic process of removing segments of premature RNA to produce mature RNA, is a key mediator of proteome diversity and regulator of gene expression. Increased systematic sequencing of the genome and transcriptome of cancers has identified a variety of means by which RNA splicin...

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Bibliographic Details
Published in:Annual review of cancer biology 2019-03, Vol.3 (1), p.167-185
Main Authors: Escobar-Hoyos, Luisa, Knorr, Katherine, Abdel-Wahab, Omar
Format: Article
Language:English
Subjects:
RNA
SF3B1
splicing
SRSF2
U2AF1
ZRSR2
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Summary:RNA splicing, the enzymatic process of removing segments of premature RNA to produce mature RNA, is a key mediator of proteome diversity and regulator of gene expression. Increased systematic sequencing of the genome and transcriptome of cancers has identified a variety of means by which RNA splicing is altered in cancer relative to normal cells. These findings, in combination with the discovery of recurrent change-of-function mutations in splicing factors in a variety of cancers, suggest that alterations in splicing are drivers of tumorigenesis. Greater characterization of altered splicing in cancer parallels increasing efforts to pharmacologically perturb splicing and early-phase clinical development of small molecules that disrupt splicing in patients with cancer. Here we review recent studies of global changes in splicing in cancer, splicing regulation of mitogenic pathways critical in cancer transformation, and efforts to therapeutically target splicing in cancer.
ISSN:2472-3428
2472-3428
DOI:10.1146/annurev-cancerbio-030617-050407