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dc.contributor.authorBillmeier, Martina
dc.contributor.authorGreen, Darrell
dc.contributor.authorHall, Adam E
dc.contributor.authorTurnbull, Carly
dc.contributor.authorSingh, Archana
dc.contributor.authorXu, Ping
dc.contributor.authorMoxon, Simon
dc.contributor.authorDalmay, Tamas
dc.date.accessioned2022-05-02T01:03:03Z
dc.date.available2022-05-02T01:03:03Z
dc.date.issued2022
dc.identifier.issn1547-6286
dc.identifier.other35354369
dc.identifier.otherPMC8973356
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336662
dc.description.abstractY RNAs (84-112 nt) are non-coding RNAs transcribed by RNA polymerase III and are characterized by a distinctive secondary structure. Human Y RNAs interact with the autoimmune proteins SSB and RO60 that together form a ribonucleoprotein (RNP) complex termed RoRNP and Y RNAs also perform regulatory roles in DNA and RNA replication and stability, which has major implications for diseases including cancer. During cellular stress and apoptosis, Y RNAs are cleaved into 3' and 5' end fragments termed Y RNA-derived small RNAs (ysRNAs). Although some ysRNA functions in stress, apoptosis and cancer have been reported, their fundamental biogenesis has not been described. Here we report that 3' end RNY5 cleavage is structure dependent. In high throughput mutagenesis experiments, cleavage occurred between the 2nd and 3rd nt above a double stranded stem comprising high GC content. We demonstrate that an internal loop above stem S3 is critical for producing 3' end ysRNAs (31 nt) with mutants resulting in longer or no ysRNAs. We show a UGGGU sequence motif at position 22 of RNY5 is critical for producing 5' end ysRNAs (22-25 nt). We show that intact RO60 is critical for ysRNA biogenesis. We conclude that ribonuclease L (RNASEL) contributes to Y RNA cleavage in mouse embryonic fibroblasts but is not the only endoribonuclease important in human cells.
dc.languageeng
dc.publisherInforma UK Limited
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101235328
dc.sourceessn: 1555-8584
dc.subjectApoptosis
dc.subjectCancer
dc.subjectSmall RNA
dc.subjectnon-coding RNA
dc.subjectY Rna
dc.subjectFibroblasts
dc.subjectAnimals
dc.subjectMice
dc.subjectRibonucleoproteins
dc.subjectRNA, Untranslated
dc.subjectRNA Processing, Post-Transcriptional
dc.subjectNucleic Acid Conformation
dc.titleMechanistic insights into non-coding Y RNA processing.
dc.typeArticle
dc.date.updated2022-05-02T01:03:03Z
prism.endingPage480
prism.issueIdentifier1
prism.publicationNameRNA Biol
prism.startingPage468
prism.volume19
dc.identifier.doi10.17863/CAM.84085
rioxxterms.versionofrecord10.1080/15476286.2022.2057725
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSingh, Archana [0000-0003-1388-9489]
dc.identifier.eissn1555-8584
cam.issuedOnline2022-03-30


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International