SIRT1 Involved in the Regulation of Alternative Splicing Affects the DNA Damage Response in Neural Stem Cells

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Guangming WangJun Xu

Abstract

Alternative splicing and DNA damage exhibit cross-regulation, with not only DNA damage inducing changes in alternative splicing, but alternative splicing itself possibly modulating the DNA damage response (DDR). Sirt1, a prominent anti-aging player, plays pivotal roles in the DDR. However, few studies have examined alternative splicing with DNA damage in neural stem cells (NSCs) and, in essence, nothing is known about whether SIRT1 regulates alternative splicing. Hence, we investigated the potential involvement of Sirt1-mediated alternative splicing in the NSC DDR. Genome-wide alternative splicing profiling was performed upon DNA damage induction and SIRT1 deletion. DNA damage caused genome-wide changes in alternative splicing in adult NSCs and Sirt1 deficiency dramatically altered DDR-related alternative splicing. In particular, extensive alternative splicing changes in DDR-related processes such as cell cycle control and DNA damage repair were observed; these processes were dramatically influenced by Sirt1 deficiency. Phenotypically, Sirt1 deficiency altered the proliferation and DNA repair of adult NSCs, possibly by regulating alternative splicing. SIRT1 helps to regulate alternative splicing, which itself affects the DDR of...Continue Reading

Citations

Mar 7, 2020·The Journal of Clinical Investigation·Manchao ZhangFen Xia
Apr 3, 2020·Genetics and Molecular Biology·Adrian E Cambindo BottoManuel J Muñoz
Feb 11, 2021·Wiley Interdisciplinary Reviews. RNA·Brittany Lynn Angarola, Olga Anczuków

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