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Cell Rep. 2014 Mar 13;6(5):906-15. doi: 10.1016/j.celrep.2014.01.037. Epub 2014 Feb 20.

RNA-DNA differences are generated in human cells within seconds after RNA exits polymerase II.

Author information

1
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
2
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
3
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
4
Cell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
6
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
7
Human Genetics Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
8
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
9
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
10
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. Electronic address: johnlis@cornell.edu.
11
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.

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.

PMID:
24561252
PMCID:
PMC4918108
DOI:
10.1016/j.celrep.2014.01.037
[Indexed for MEDLINE]
Free PMC Article

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