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

• 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
• ISSN: 2211-1247

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.