Pre-mRNA splicing-associated diseases and therapies

被引：22

作者：

Love, Sierra L. L. ^{[1
,2
]}

Emerson, Joseph D. D. ^{[3
]}

Koide, Kazunori ^{[3
]}

Hoskins, Aaron A. A. ^{[2
,4
]}

机构：

[1] Univ Wisconsin, Genet Training Program, Madison, WI 53706 USA

[2] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

[3] Univ Pittsburgh, Dept Chem, Pittsburgh, PA USA

[4] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

来源：

RNA BIOLOGY | 2023年 / 20卷 / 01期

基金：

美国国家卫生研究院;

关键词：

spliceosome; pre-mRNA splicing; cancer; SMA; spliceosomopathy; snRNA; splicing inhibitor; splicing modulator; DOMINANT RETINITIS-PIGMENTOSA; FACTOR CAPER-ALPHA; SMALL NUCLEAR-RNA; STRUCTURAL BASIS; MINOR SPLICEOSOME; RBM39; RECRUITMENT; CATALYTIC STEPS; SITE SELECTION; IN-VITRO; MUTATIONS;

D O I：

10.1080/15476286.2023.2239601

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Precursor mRNA (pre-mRNA) splicing is an essential step in human gene expression and is carried out by a large macromolecular machine called the spliceosome. Given the spliceosome's role in shaping the cellular transcriptome, it is not surprising that mutations in the splicing machinery can result in a range of human diseases and disorders (spliceosomopathies). This review serves as an introduction into the main features of the pre-mRNA splicing machinery in humans and how changes in the function of its components can lead to diseases ranging from blindness to cancers. Recently, several drugs have been developed that interact directly with this machinery to change splicing outcomes at either the single gene or transcriptome-scale. We discuss the mechanism of action of several drugs that perturb splicing in unique ways. Finally, we speculate on what the future may hold in the emerging area of spliceosomopathies and spliceosome-targeted treatments.

引用

页码：525 / 538

页数：14

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