NBS1 facilitates preribosomal RNA biogenesis

• 成果类型: Article
• 署名作者: Luo, Man; Yu, Xiaochun
• 署名单位: Fudan University; Westlake Laboratory; Westlake University; Westlake University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8510
• DOI: 10.1073/pnas.2422029122
• 发表日期: 2025-03-18
• 关键词: nijmegen breakage syndrome; polymerase i transcription; crest cell-formation; ataxia-telangiectasia; ribosome biogenesis; syndrome gene; dna-repair; activation; protein; atm

摘要

Mutations in the NBS1 gene result in Nijmegen breakage syndrome (NBS), and the gene encodes NBS1 that forms a complex with MRE11 and RAD50 and participates in DNA damage repair. However, the molecular mechanism by which NBS1 mutations cause clinical phenotypes of NBS, such as craniofacial dysmorphism, is still unclear. Here, we show that NBS1 localizes at the ribosomal DNA (rDNA) loci in nucleoli and interacts with ribosomal RNA (rRNA) transcription machinery including RNA polymerase I (PolI) and TCOF1. Loss of NBS1 impairs PolI-dependent transcription of pre-rRNA and induces nucleolar stress. In particular, lacking Nbs1 in mouse neural crest cells not only leads to the reduction of ribosome biogenesis but also craniofacial abnormalities during prenatal development. Moreover, the C-terminus of NBS1 associated with pre-rRNA and a number of pre-rRNA processing factors, which may also facilitate pre-rRNA maturation. Taken together, our study reveals the functions of NBS1 in rRNA biogenesis.