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dc.contributor.authorTorres Ulloa, Leslie
dc.contributor.authorCalvo-Roitberg, Ezequiel
dc.contributor.authorPai, Athma A
dc.date.accessioned2024-04-03T14:30:57Z
dc.date.available2024-04-03T14:30:57Z
dc.date.issued2024-02-16
dc.identifier.citationTorres-Ulloa L, Calvo-Roitberg E, Pai AA. Genome-wide kinetic profiling of pre-mRNA 3' end cleavage. RNA. 2024 Feb 16;30(3):256-270. doi: 10.1261/rna.079783.123. PMID: 38164598; PMCID: PMC10870368.en_US
dc.identifier.eissn1469-9001
dc.identifier.doi10.1261/rna.079783.123en_US
dc.identifier.pmid38164598
dc.identifier.urihttp://hdl.handle.net/20.500.14038/53264
dc.description.abstractCleavage and polyadenylation is necessary for the formation of mature mRNA molecules. The rate at which this process occurs can determine the temporal availability of mRNA for subsequent function throughout the cell and is likely tightly regulated. Despite advances in high-throughput approaches for global kinetic profiling of RNA maturation, genome-wide 3' end cleavage rates have never been measured. Here, we describe a novel approach to estimate the rates of cleavage, using metabolic labeling of nascent RNA, high-throughput sequencing, and mathematical modeling. Using in silico simulations of nascent RNA-seq data, we show that our approach can accurately and precisely estimate cleavage half-lives for both constitutive and alternative sites. We find that 3' end cleavage is fast on average, with half-lives under a minute, but highly variable across individual sites. Rapid cleavage is promoted by the presence of canonical sequence elements and an increased density of polyadenylation signals near a cleavage site. Finally, we find that cleavage rates are associated with the localization of RNA polymerase II at the end of a gene, and faster cleavage leads to quicker degradation of downstream readthrough RNA. Our findings shed light on the features important for efficient 3' end cleavage and the regulation of transcription termination.en_US
dc.language.isoenen_US
dc.relation.ispartofRNAen_US
dc.relation.urlhttps://doi.org/10.1261/rna.079783.123en_US
dc.rights© 2024 Torres-Ulloa et al. This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/ by-nc/4.0/.en_US
dc.rightsAttribution-NonCommercial 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectRNA processingen_US
dc.subjectcleavage and polyadenylationen_US
dc.subjectgenomicsen_US
dc.titleGenome-wide kinetic profiling of pre-mRNA 3' end cleavageen_US
dc.typeJournal Articleen_US
dc.source.journaltitleRNA (New York, N.Y.)
dc.source.volume30
dc.source.issue3
dc.source.beginpage256
dc.source.endpage270
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalRNA (New York, N.Y.)
refterms.dateFOA2024-04-03T14:30:59Z
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.contributor.departmentRNA Therapeutics Instituteen_US
dc.contributor.studentLeslie Torres-Ulloa
dc.contributor.studentEzequiel Calvo-Roitberg
dc.description.thesisprogramInterdisciplinary Graduate Program


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© 2024 Torres-Ulloa et al. This article, published in RNA, is available
under a Creative Commons License (Attribution-NonCommercial 4.0
International), as described at http://creativecommons.org/licenses/
by-nc/4.0/.
Except where otherwise noted, this item's license is described as © 2024 Torres-Ulloa et al. This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/ by-nc/4.0/.