A novel lncRNA Discn fine-tunes replication protein A (RPA) availability to promote genomic stability.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34552092.
- Also identified by DOI 10.1038/s41467-021-25827-6 and PMC identifier 8458541.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
RPA is a master regulator of DNA metabolism and RPA availability acts as a rate-limiting factor. While numerous studies focused on the post-translational regulations of RPA for its functions, little is known regarding how RPA availability is controlled. Here we identify a novel lncRNA Discn as the guardian of RPA availability in stem cells. Discn is induced upon genotoxic stress and binds to neucleolin (NCL) in the nucleolus. This prevents NCL from translocation into nucleoplasm and avoids undesirable NCL-mediated RPA sequestration. Thus, Discn-NCL-RPA pathway preserves a sufficient RPA pool for DNA replication stress response and repair. Discn loss causes massive genome instability in mouse embryonic stem cells and neural stem/progenigor cells. Mice depleted of Discn display newborn death and brain dysfunctions due to DNA damage accumulation and associated inflammatory reactions. Our findings uncover a key regulator of DNA metabolism and provide new clue to understand the chemoresistance in cancer treatment.
Medical subject headings
- Genomic Instability
- RNA, Long Noncoding
- Replication Protein A