The high frequency of DNA damage necessitates effective repair mechanisms. Evidence is mounting that RNA plays an important role in DNA repair. Dr. Woan-Yuh Tarn’s research group identified the long non-coding RNA (lncRNA) HOTAIRM1 via its association with the RNA processing factor Y14. HOTAIRM1 also interacts with the DNA repair factors involved in nonhomologous end joining (NHEJ) of DNA double strand break (DSB). Depletion of HOTAIRM1 resulted in delayed recruitment of DNA repair factors to DNA damage sites and compromised NHEJ-mediated DSB repair. Moreover, HOTAIRM1 brings mRNA surveillance factors to DNA damage sites, which degrade DSB-induced non-coding transcripts. Such RNA clearance may accelerate the turnover of DNA repair factors, leading to efficient repair. Together, this study identified a lncRNA ribonucleoprotein complex that participates in DNA damage repair.
In another study, Dr. Tarn’s group found that Y14 undergoes phase separation to form liquid-like droplets in vitro via its multivalent electrostatic interactions. Domain mapping revealed that a greater net positive charge of Y14 promoted its LLPS. Moreover, Y14 co-phase separates with synthetic RNA homopolymers or HOTAIRM1. RNA modulates Y14 LLPS in a concentration-dependent manner. Finally, this study revealed that the LLPS capacity of Y14 appears to be important for its activity in DNA repair repair. This study implies that co-condensation of Y14 with non-coding RNAs is essential for genome stability.
The above two studies are respectively published in Nucleic Acids Research (Article online https://doi.org/10.1093/nar/gkad143, March 07, 2023; the first author, Tzu-Wei Chuang, is currently a postdoctoral fellow), and RNA (Published in Advance, doi:10.1261/rna.079514.122, March 31, 2023; the first author, Chia-Ling Yu was a research assistant). This work was supported by Academia Sincia and National Science and Technology Council.
Dr. Woan-Yuh Tarn (corresponding author)
Distinguished Research Fellow in the Institute of Biomedical Sciences, Academia Sinica
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