Proteomics

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LncRNA HOTAIRM1 Coordinates with RNA Processing Factors in DNA Damage Repair

ABSTRACT: The eukaryotic RNA processing factor Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. We identified the long non-coding RNA HOTAIRM1 as a candidate that mediates this interaction. HOTAIRM1 localized to DNA damage sites induced by ionizing radiation. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and reduced DNA repair efficiency. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and RNA processing factors that act in concert to repair DSBs.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Fu-An Li  

LAB HEAD: Woan-Yuh Tarn

PROVIDER: PXD034470 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors.

Chuang Tzu-Wei TW   Su Chun-Hao CH   Wu Pei-Yu PY   Chang Yao-Ming YM   Tarn Woan-Yuh WY  

Nucleic acids research 20230401 7

The eukaryotic exon junction complex component Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. Using immunoprecipitation-RNA-seq, we identified a set of Y14-associated long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1 serves as a strong candidate that mediates the interaction between Y14 and the NHEJ complex. HOTAIRM1 localized to near ultraviolet laser-induced DNA damage sites. Depletion of HOTAIRM1 del  ...[more]

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