title: RNA-DNA differences are generated in human cells within seconds after RNA exits polymerase II.
abstract: RNA sequences are expected to be identical to their corresponding DNA sequences. Here, we found all 12 types of RNA-DNA sequence differences (RDDs) in nascent RNA. Our results show that RDDs begin to occur in RNA chains ~55 nt from the RNA polymerase II (Pol II) active site. These RDDs occur so soon after transcription that they are incompatible with known deaminase-mediated RNA-editing mechanisms. Moreover, the 55 nt delay in appearance indicates that they do not arise during RNA synthesis by Pol II or as a direct consequence of modified base incorporation. Preliminary data suggest that RDD and R-loop formations may be coupled. These findings identify sequence substitution as an early step in cotranscriptional RNA processing.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Isabel X
authors.initials: IX
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Leighton J
authors.initials: LJ
authors.lastname: Core
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kwak
authors.affiliation: Cell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brady
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Bruzel
authors.affiliation: Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: McDaniel
authors.affiliation: Human Genetics Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Richards
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grunseich
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: johnlis@cornell.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Departments of Pediatrics and Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: vgcheung@umich.edu.
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Cheung
mesh_terms: D020134:Catalytic Domain; D018929:Cell Culture Techniques; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012313:RNA; D004247:DNA; D012319:RNA Polymerase II