NBS1 facilitates pre-ribosomal RNA biogenesis

Mutations of 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 the mutations of NBS1 cause clinical phenotypes of NBS, such as craniofacial dysmorphism, is still unclear. Here, we show that NBS1 localizes at the rDNA loci in the nucleoli and interacts with ribosome RNA (rRNA) transcription machinery including RNA polymerase I (Pol I) and TCOF1. Loss of NBS1 impairs Pol I-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 is 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.