A transcription‐independent mechanism determines rapid periodic fluctuations of BRCA1 expression

BRCA1 expression is highly regulated to prevent genomic instability and tumorigenesis. Dysregulation of BRCA1 expression correlates closely with sporadic basal‐like breast cancer and ovarian cancer. The most significant characteristic of BRCA1 regulation is periodic expression fluctuation throughout the cell cycle, which is important for the orderly progression of different DNA repair pathways throughout the various cell cycle phases and for further genomic stability. However, the underlying mechanism driving this phenomenon is poorly understood. Here, we demonstrate that RBM10‐mediated RNA alternative splicing coupled to nonsense‐mediated mRNA decay (AS‐NMD), rather than transcription, determines the periodic fluctuations in G1/S‐phase BRCA1 expression. Furthermore, AS‐NMD broadly regulates the expression of period genes, such as DNA replication‐related genes, in an uneconomical but more rapid manner. In summary, we identified an unexpected posttranscriptional mechanism distinct from canonical processes that mediates the rapid regulation of BRCA1 as well as other period gene expression during the G1/S‐phase transition and provided insights into potential targets for cancer therapy.

• Publication year

  2023

• Venue

  EMBO Journal

• Publication date

  2023-06-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.15252/embj.2022111951PMID 37334492PMCID PMC10390875
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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