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

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.