A disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis.

ABSTRACT: RMRP encodes a non-coding RNA forming the core of the RNase MRP ribonucleoprotein complex. Mutations cause Cartilage Hair Hypoplasia (CHH), characterized by skeletal abnormalities and impaired T cell activation. Yeast RNase MRP cleaves a specific site in the pre-ribosomal RNA (pre-rRNA) during ribosome synthesis. CRISPR-mediated disruption of RMRP in human cells lines caused growth arrest, with pre-rRNA accumulation. Here, we analyzed disease-relevant primary cells, showing that mutations in RMRP impair mouse T cell activation and delay pre-rRNA processing. Patient-derived human fibroblasts with CHH-linked mutations showed similar pre-rRNA processing delay. Human cells engineered with the most common CHH mutation (70^AG in RMRP) show specifically impaired pre-rRNA processing, res

SUBMITTER: Robertson N 

PROVIDER: S-EPMC8814244 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature