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mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global

Tobias D Williams1, Ewa M Michalak2, Kirstyn T Carey2

  • 1Friedrich Miescher Institute for Biomedical Research, 4056 Basel, Switzerland; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Molecular Cell
|January 3, 2025
PubMed

Insights

Potent transcription inhibitors disrupt mRNA localization and nuclear export, causing transcripts to accumulate in nuclear speckles. This adaptive response impacts cancer therapy development by revealing new insights into transcription-mRNA export crosstalk.

Area of Science:

  • Molecular Biology
  • Cancer Therapeutics
  • Cellular Biology

Background:

  • Transcription inhibitors are used in cancer therapy but have limited efficacy.
  • Current understanding of cellular responses to transcriptional inhibition is incomplete.

Purpose of the Study:

  • To investigate the effects of transcription inhibitors beyond mRNA output.
  • To elucidate the role of mRNA localization and nuclear export in response to transcriptional inhibition.

Main Methods:

  • Utilized potent transcription inhibitors in cellular models.
  • Analyzed mRNA transcript localization and nuclear export dynamics.
  • Investigated the involvement of the TREX mRNA export complex and NXF1.

Main Results:

  • Transcription inhibitors impair mRNA transcript localization and nuclear export.
  • Newly transcribed mRNA is retained in nuclear speckles as an adaptive response.
  • The TREX complex and NXF1 are crucial for transcript retention and subsequent export.

Conclusions:

  • Transcriptional inhibition affects mRNA processing, localization, and export.
  • Understanding this crosstalk is vital for developing effective cancer therapeutics.
  • Findings offer new therapeutic strategies targeting transcription-export pathways.
Keywords:
BET degraderDRBNXF1Nuclear exportTREXepigenetic drugsmRNA localisationnuclear specklestranscription

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