In:
The EMBO Journal, EMBO, Vol. 42, No. 15 ( 2023-08)
Abstract:
image How expression of BRCA1 is dynamically regulated throughout the cell cycle in cancer cells remains unclear. This study uncovers a critical role for RBM10‐mediated RNA alternative splicing coupled to nonsense‐mediated mRNA decay (AS‐NMD) in determining periodic BRCA1 fluctuations in G1/S‐phase. CDK2‐RBM10‐mediated AS‐NMD determines periodic BRCA1 mRNA expression during the G1/S transition. AS‐NMD‐mediated periodic expression regulation controls gene periodic fluctuations during G1/S transition by altering the proportion of mRNAs degraded while remaining transcriptionally active. Rapid AS‐NMD organizes periodic gene expression throughout the cell cycle. Combination of CDK2 inhibitors with PARP inhibitors is a potential therapeutic strategy.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.2022111951
Language:
English
Publisher:
EMBO
Publication Date:
2023
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12
