RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II

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...

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Main Authors: Isabel X. Wang, Leighton J. Core, Hojoong Kwak, Lauren Brady, Alan Bruzel, Lee McDaniel, Allison L. Richards, Ming Wu, Christopher Grunseich, John T. Lis, Vivian G. Cheung
Format: Article
Language:English
Published: Elsevier 2014-03-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124714000710
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spelling doaj-5f2aebfb28ce422f95afdc0f229f309e2020-11-25T01:46:35ZengElsevierCell Reports2211-12472014-03-016590691510.1016/j.celrep.2014.01.037RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase IIIsabel X. Wang0Leighton J. Core1Hojoong Kwak2Lauren Brady3Alan Bruzel4Lee McDaniel5Allison L. Richards6Ming Wu7Christopher Grunseich8John T. Lis9Vivian G. Cheung10Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USADepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USACell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USALife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USAHuman Genetics Graduate Program, University of Michigan, Ann Arbor, MI 48109, USAHoward Hughes Medical Institute, Chevy Chase, MD 20815, USANeurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USADepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USALife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USARNA 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.http://www.sciencedirect.com/science/article/pii/S2211124714000710
collection DOAJ
language English
format Article
sources DOAJ
author Isabel X. Wang
Leighton J. Core
Hojoong Kwak
Lauren Brady
Alan Bruzel
Lee McDaniel
Allison L. Richards
Ming Wu
Christopher Grunseich
John T. Lis
Vivian G. Cheung
spellingShingle Isabel X. Wang
Leighton J. Core
Hojoong Kwak
Lauren Brady
Alan Bruzel
Lee McDaniel
Allison L. Richards
Ming Wu
Christopher Grunseich
John T. Lis
Vivian G. Cheung
RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II
Cell Reports
author_facet Isabel X. Wang
Leighton J. Core
Hojoong Kwak
Lauren Brady
Alan Bruzel
Lee McDaniel
Allison L. Richards
Ming Wu
Christopher Grunseich
John T. Lis
Vivian G. Cheung
author_sort Isabel X. Wang
title RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II
title_short RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II
title_full RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II
title_fullStr RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II
title_full_unstemmed RNA-DNA Differences Are Generated in Human Cells within Seconds after RNA Exits Polymerase II
title_sort rna-dna differences are generated in human cells within seconds after rna exits polymerase ii
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2014-03-01
description 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.
url http://www.sciencedirect.com/science/article/pii/S2211124714000710
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