Transcription-replication conflict resolution by nuclear RNA interference

Cheng, Teri, Roche, Benjamin, Abderahmane, Farida, Touat-Todeschini, Leila, Fréon, Karine, Lakhani, Asad A, Bhattacharjee, Sonali, Spielmann, Liam G, Jenen, Emerson, Choi, Christine, Ren, Jie, Verdel, André, Lambert, Sarah AE, Martienssen, Robert A (October 2025) Transcription-replication conflict resolution by nuclear RNA interference. Molecular Cell. ISSN 1097-2765 (Public Dataset)

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Abstract

Nuclear RNA interference (RNAi) is required for heterochromatin silencing, but Dicer also promotes genome stability by releasing RNA polymerase at sites of replication stress. R-loops are three-stranded DNA:RNA structures that accumulate at transcription-replication (T-R) collisions. We show that in RNase H-deficient cells, which accumulate pathological R-loops, Dcr1 processes R-loops at transcriptional start sites (TSSs) and end sites (TESs), releasing paused RNA polymerase and accounting for small RNAs (sRNAs) resembling DNA-damage-associated sense sRNAs (sdRNAs) found in cancer cells. Genetic evidence implicates nascent transcription-associated R-loops in genome instability in the absence of Dicer, with the helicase domain providing catalytic function reminiscent of related archaeal helicases involved in replication. The RNase H homolog Argonaute (Ago1) promotes genome instability by binding R-loops, and its removal relieves replication stress. Analysis of replication intermediates, DNA and RNA 3' ends, and fork processivity genome wide indicates Dicer resolves head-on T-R collisions, consistent with an ancient origin in DNA replication.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Inheritance Program
CSHL labs > Martienssen lab
CSHL Post Doctoral Fellows
School of Biological Sciences > Publications
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 28 October 2025
Date Deposited: 30 Oct 2025 14:06
Last Modified: 30 Oct 2025 14:06
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/41996

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