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dc.contributor.authorLoughran, Gary
dc.contributor.authorJungreis, Irwin
dc.contributor.authorTzani, Ioanna
dc.contributor.authorPower, Michael
dc.contributor.authorDmitriev, Ruslan I
dc.contributor.authorIvanov, Ivaylo P
dc.contributor.authorKellis, Manolis
dc.contributor.authorAtkins, John F
dc.date.accessioned2022-07-11T16:05:00Z
dc.date.available2021-10-27T19:58:26Z
dc.date.available2022-07-11T16:05:00Z
dc.date.issued2018
dc.identifier.urihttps://hdl.handle.net/1721.1/134162.2
dc.description.abstract© 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Although stop codon readthrough is used extensively by viruses to expand their gene expression, verified instances of mammalian readthrough have only recently been uncovered by systems biology and comparative genomics approaches. Previously, our analysis of conserved protein coding signatures that extend beyond annotated stop codons predicted stop codon readthrough of several mammalian genes, all of which have been validated experimentally. Four mRNAs display highly efficient stop codon readthrough, and these mRNAs have a UGA stop codon immediately followed by CUAG (UGA_CUAG) that is conserved throughout vertebrates. Extending on the identification of this readthrough motif, we here investigated stop codon readthrough, using tissue culture reporter assays, for all previously untested human genes containing UGA_CUAG. The readthrough efficiency of the annotated stop codon for the sequence encoding vitamin D receptor (VDR) was 6.7%. It was the highest of those tested but all showed notable levels of readthrough. The VDR is a member of the nuclear receptor superfamily of ligand-inducible transcription factors, and it binds its major ligand, calcitriol, via its C-terminal ligand-binding domain. Readthrough of the annotated VDR mRNA results in a 67 amino acid–long C-terminal extension that generates a VDR proteoform named VDRx. VDRx May form homodimers and heterodimers with VDR but, compared with VDR, VDRx displayed a reduced transcriptional response to calcitriol even in the presence of its partner retinoid X receptor.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1074/JBC.M117.818526en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceAmerican Society for Biochemistry and Molecular Biologyen_US
dc.titleStop codon readthrough generates a C-terminally extended variant of the human vitamin D receptor with reduced calcitriol responseen_US
dc.typeArticleen_US
dc.contributor.departmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratoryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.relation.journalJournal of Biological Chemistryen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2019-06-07T15:02:13Z
dspace.orderedauthorsLoughran, G; Jungreis, I; Tzani, I; Power, M; Dmitriev, RI; Ivanov, IP; Kellis, M; Atkins, JFen_US
dspace.date.submission2019-06-07T15:02:15Z
mit.journal.volume293en_US
mit.journal.issue12en_US
mit.metadata.statusPublication Information Neededen_US


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