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Modified Y RNA-derived fragments form a complex with YBX1 and PARP1 to promote DNA repair

ABSTRACT: To protect genome integrity from pervasive threats of damage and prevent diseases like cancer, cells employ an integrated network of signalling pathways called the DNA damage response. These pathways involve both protein and RNA components which can act within the damaged cell or be transferred intercellularly to influence population-wide responses to damage. Here, we show that radioprotection can be conferred by damage-derived exosomes and is dependent on YBX1-packaged Y3-derived ysRNA. These ysRNA enter the nucleus of bystander cells upon DNA damage to become methylated by NSUN2. This allows interaction with YBX1 at double strand break (DSB) sites to promote efficient DNA repair and cell survival through complex formation with PARP1. YBX1 facilitates increased PARP1 auto-modification and ADP-ribosylation of ysRNA, promoting increased PARP1 residency at DSBs. We therefore highlight a new role for these under-studied species of small non-coding RNA in DNA repair.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269346 | GEO | 2025/07/02

REPOSITORIES: GEO

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