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Updated: Jun 6, 2026

Live-Cell Imaging of Transcriptional Activity at DNA Double-Strand Breaks
09:07

Live-Cell Imaging of Transcriptional Activity at DNA Double-Strand Breaks

Published on: September 20, 2021

rDNA breaks activate dsRNA pattern recognition through sense-antisense transcription

Jie Chen, Sangin Kim, Sixing Chen

    Biorxiv : the Preprint Server for Biology
    |June 5, 2026
    PubMed

    Insights

    DNA damaging therapies create abnormal ribosomal RNA (rRNA) transcripts that trigger immune responses via MDA5 and RIG-I. This links nucleolar stress to immune signaling, revealing consequences of DNA damage.

    Area of Science:

    • Molecular Biology
    • Immunology
    • Genetics

    Background:

    • Chemo- and radio- therapies damage DNA, impacting ribosomal RNA (rRNA) transcription and processing.
    • The biological outcomes of these rRNA processing disruptions are not fully understood.

    Purpose of the Study:

    • To investigate the consequences of DNA damage on rRNA transcription and processing.
    • To elucidate the mechanism by which aberrant rRNA species activate immune signaling pathways.

    Main Methods:

    • Analysis of aberrant rRNA transcripts generated from DNA breaks.
    • Investigating the engagement of double-stranded RNA pattern recognition receptors (MDA5 and RIG-I).
    • Purification of endogenous MDA5-filaments and sequencing.

    Main Results:

    • DNA damage leads to truncated sense-antisense rRNA transcripts instead of full-length rRNA.
    • These aberrant rRNA transcripts activate immune signaling via MDA5 and RIG-I.
    • ATM and ATR kinase activities regulate the accumulation of these truncated rRNA species.

    Conclusions:

    • Aberrant rRNA transcripts serve as endogenous ligands that activate dsRNA pattern recognition receptors following DNA damage.
    • A novel mechanism links nucleolar stress, induced by DNA damage, to the activation of innate immune signaling.

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