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Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited ANKRD1 mRNA Stabilization

Chang Hoon Shin1, Martina Rossi1, Carlos Anerillas1

  • 1Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.

Molecular and Cellular Biology
|May 21, 2024
PubMed

Insights

Cellular senescence involves increased ANKRD1 protein. The RNA-binding protein RBMS1 stabilizes ANKRD1 mRNA, boosting its production during early senescence.

Area of Science:

  • Cellular and Molecular Biology
  • Gene Regulation
  • Aging Research

Background:

  • Cellular senescence is a state of irreversible cell cycle arrest.
  • ANKRD1 (ankyrin repeat domain 1) protein levels increase during senescence.
  • Mechanisms regulating ANKRD1 production in early senescence are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms driving elevated ANKRD1 production in early senescence.
  • To identify proteins interacting with ANKRD1 mRNA.
  • To investigate the role of RBMS1 in ANKRD1 regulation.

Main Methods:

  • Etoposide (Eto) treatment to induce senescence in fibroblasts.
  • Analysis of ANKRD1 mRNA and protein levels.
  • Antisense oligomer (ASO) pulldown and mass spectrometry.
  • Ribonucleoprotein immunoprecipitation (RIP) analysis.
  • RBMS1 silencing and overexpression studies.
  • Reporter gene assays.

Main Results:

  • Etoposide-induced senescence increased ANKRD1 via moderate transcription/translation and robust mRNA stabilization.
  • RBMS1 specifically binds to ANKRD1 mRNA.
  • RBMS1 cellular localization shifts from nucleus to cytoplasm during senescence.
  • RBMS1 depletion reduced ANKRD1 mRNA half-life; RBMS1 overexpression enhanced it.
  • A specific region of ANKRD1 mRNA mediates RBMS1 binding and expression.

Conclusions:

  • RBMS1 stabilizes ANKRD1 mRNA during early etoposide-induced senescence.
  • RBMS1 plays a key role in the post-transcriptional regulation of ANKRD1.
  • This mechanism contributes to elevated ANKRD1 levels in senescent cells.
Keywords:
RNA-binding proteinpost-transcriptional gene regulationsenescence

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