Targeting serine- and arginine-rich splicing factors to rectify aberrant alternative splicing

Dianyang Li; Wenying Yu; Maode Lai

doi:10.1016/j.drudis.2023.103691

Targeting serine- and arginine-rich splicing factors to rectify aberrant alternative splicing

Drug Discov Today. 2023 Sep;28(9):103691. doi: 10.1016/j.drudis.2023.103691. Epub 2023 Jun 27.

Authors

Dianyang Li¹, Wenying Yu², Maode Lai³

Affiliations

¹ Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
² State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
³ Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China; Department of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Science (2019RU042), Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China. Electronic address: [email protected].

PMID: 37385370
DOI: 10.1016/j.drudis.2023.103691

Abstract

Serine- and arginine-rich splicing factors are pivotal modulators of constitutive splicing and alternative splicing that bind to the cis-acting elements in precursor mRNAs and facilitate the recruitment and assembly of the spliceosome. Meanwhile, SR proteins shuttle between the nucleus and cytoplasm with a broad implication in multiple RNA-metabolizing events. Recent studies have demonstrated the positive correlation of overexpression and/or hyperactivation of SR proteins and development of the tumorous phenotype, indicating the therapeutic potentials of targeting SR proteins. In this review, we highlight key findings concerning the physiological and pathological roles of SR proteins. We have also investigated small molecules and oligonucleotides that effectively modulate the functions of SR proteins, which could benefit future studies of SR proteins.

Keywords: Alternative splicing; SR proteins; cancers; drug development; oligonucleotides; splicing factors.

Publication types

Review

MeSH terms

Alternative Splicing* / genetics
Arginine* / metabolism
Nuclear Proteins / metabolism
RNA Splicing Factors / genetics
RNA Splicing Factors / metabolism
RNA-Binding Proteins / metabolism
Serine / genetics
Serine / metabolism
Serine-Arginine Splicing Factors / genetics
Serine-Arginine Splicing Factors / metabolism

Substances

RNA Splicing Factors
Arginine
Serine
RNA-Binding Proteins
Serine-Arginine Splicing Factors
Nuclear Proteins