Alternative pre-mRNA splicing in stem cell function and therapeutic potential: A critical review of current evidence

• Published in: International journal of biological macromolecules Vol. 268; no. Pt 1; p. 131781
• Main Authors: Cui, Li, Zheng, Yucheng, Xu, Rongwei, Lin, Yunfan, Zheng, Jiarong, Lin, Pei, Guo, Bing, Sun, Shuyu, Zhao, Xinyuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2024
• Subjects: Alternative Splicing; Animals; Cell Differentiation - genetics; Differentiation; Humans; RNA Precursors - genetics; RNA Precursors - metabolism; Splicing factor; Stem cell; Stem Cells - cytology; Stem Cells - metabolism; Therapeutic potential; Alternative splicing; Differentiation; Therapeutic potential; Splicing factor; Stem cell
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.131781

Alternative splicing is a crucial regulator in stem cell biology, intricately influencing the functions of various biological macromolecules, particularly pre-mRNAs and the resultant protein isoforms. This regulatory mechanism is vital in determining stem cell pluripotency, differentiation, and proliferation. Alternative splicing's role in allowing single genes to produce multiple protein isoforms facilitates the proteomic diversity that is essential for stem cells' functional complexity. This review delves into the critical impact of alternative splicing on cellular functions, focusing on its interaction with key macromolecules and how this affects cellular behavior. We critically examine how alternative splicing modulates the function and stability of pre-mRNAs, leading to diverse protein expressions that govern stem cell characteristics, including pluripotency, self-renewal, survival, proliferation, differentiation, aging, migration, somatic reprogramming, and genomic stability. Furthermore, the review discusses the therapeutic potential of targeting alternative splicing-related pathways in disease treatment, particularly focusing on the modulation of RNA and protein interactions. We address the challenges and future prospects in this field, underscoring the need for further exploration to unravel the complex interplay between alternative splicing, RNA, proteins, and stem cell behaviors, which is crucial for advancing our understanding and therapeutic approaches in regenerative medicine and disease treatment.