Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects

被引：132

作者：

Rogalska, Malgorzata Ewa ^{[1
]}

Vivori, Claudia ^{[1
,2
,4
]}

Valcarcel, Juan ^{[1
,2
,3
]}

机构：

[1] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Genome Biol Program, Barcelona, Spain

[2] Univ Pompeu Fabra UPF, Dept Med & Life Sci, Barcelona, Spain

[3] Institucio Catalana Recerca i Estudis Avancats ICR, Barcelona, Spain

[4] Francis Crick Inst, London, England

来源：

NATURE REVIEWS GENETICS | 2023年 / 24卷 / 04期

基金：

欧洲研究理事会;

关键词：

NON-B DNA; NUCLEOTIDE EXCISION-REPAIR; SPINAL MUSCULAR-ATROPHY; HUMAN C-MYC; TRINUCLEOTIDE REPEAT INSTABILITY; TRIPLEX-FORMING OLIGONUCLEOTIDES; MYOTONIC-DYSTROPHY PATIENTS; POLYMERASE-II ELONGATION; G-QUADRUPLEX STRUCTURES; REPLICATION PROTEIN-A;

D O I：

10.1038/s41576-022-00556-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The removal of introns from mRNA precursors and its regulation by alternative splicing are key for eukaryotic gene expression and cellular function, as evidenced by the numerous pathologies induced or modified by splicing alterations. Major recent advances have been made in understanding the structures and functions of the splicing machinery, in the description and classification of physiological and pathological isoforms and in the development of the first therapies for genetic diseases based on modulation of splicing. Here, we review this progress and discuss important remaining challenges, including predicting splice sites from genomic sequences, understanding the variety of molecular mechanisms and logic of splicing regulation, and harnessing this knowledge for probing gene function and disease aetiology and for the design of novel therapeutic approaches.

引用

页码：251 / 269

页数：19

共 316 条

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