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dc.contributor.authorRobertson, Nic
dc.contributor.authorShchepachev, Vadim
dc.contributor.authorWright, David
dc.contributor.authorTurowski, Tomasz W
dc.contributor.authorSpanos, Christos
dc.contributor.authorHelwak, Aleksandra
dc.contributor.authorZamoyska, Rose
dc.contributor.authorTollervey, David
dc.date.accessioned2022-02-03T16:34:55Z
dc.date.available2022-02-03T16:34:55Z
dc.date.issued2022-02-03
dc.date.submitted2021-05-03
dc.identifier.issn2041-1723
dc.identifier.others41467-022-28295-8
dc.identifier.other28295
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333601
dc.description.abstractRMRP 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 (70AG in RMRP) show specifically impaired pre-rRNA processing, resulting in reduced mature rRNA and a reduced ratio of cytosolic to mitochondrial ribosomes. Moreover, the 70AG mutation caused a reduction in intact RNase MRP complexes. Together, these results indicate that CHH is a ribosomopathy.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/208/200
dc.subject/631/80/304
dc.subject/631/250/2502
dc.subject/631/1647/2017/2003
dc.subject/631/337/384/2568
dc.subject/38
dc.subject/38/90
dc.subject/38/91
dc.subject/49
dc.subject/13/31
dc.subject/42/41
dc.subject/82/58
dc.subject/13
dc.subject/13/106
dc.subjectarticle
dc.titleA disease-linked lncRNA mutation in RNase MRP inhibits ribosome synthesis.
dc.typeArticle
dc.date.updated2022-02-03T16:34:53Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.81017
dcterms.dateAccepted2022-01-14
rioxxterms.versionofrecord10.1038/s41467-022-28295-8
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidShchepachev, Vadim [0000-0001-8551-5940]
dc.contributor.orcidTurowski, Tomasz W [0000-0002-7052-8682]
dc.contributor.orcidSpanos, Christos [0000-0002-4376-8242]
dc.contributor.orcidZamoyska, Rose [0000-0001-9816-2638]
dc.contributor.orcidTollervey, David [0000-0003-2894-2772]
dc.identifier.eissn2041-1723
pubs.funder-project-idWellcome Trust (Wellcome) (205014, 077248, 203149)
cam.issuedOnline2022-02-03


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