Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA
By Jeffrey E. Squires, Hardip R. Patel, Marco Nousch, Tennille Sibbritt, D. Humphreys, B. Parker, C. Suter, T. Preiss. Nucleic Acids Research, 2012
897 citations recorded by the source corpus.
The modified base 5-methylcytosine (m5C) is well studied in DNA, but investigations of its prevalence in cellular RNA have been largely confined to tRNA and rRNA. In animals, the two m5C methyltransferases NSUN2 and TRDMT1 are known to modify specific tRNAs and have roles in the control of cell growth and differentiation. To map modified cytosine sites across a human transcriptome, we coupled bisulfite conversion of cellular RNA with next-generation sequencing. We confirmed 21 of the 28 previously known m5C sites in human tRNAs and identified 234 novel tRNA candidate sites, mostly in anticipated structural positions. Surprisingly, we discovered 10 275 sites in mRNAs and other non-coding RNAs. We observed that distribution of modified cytosines between RNA types was not random; within mRNAs they were enriched in the untranslated regions and near Argonaute binding regions. We also identified five new sites modified by NSUN2, broadening its known substrate range to another tRNA, the RPPH1 subunit of RNase P and two mRNAs. Our data demonstrates the widespread presence of modified cytosines throughout coding and non-coding sequences in a transcriptome, suggesting a broader role of this modification in the post-transcriptional control of cellular RNA function.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/99442081dbff48d9574818cc4a808c79dfe55acb
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Citations in the corpus
- The mysterious presence of a 5-methylcytosine oxidase in the Drosophila genome (2013, background): “However, there is widespread presence of 5mC not only in tRNA, but also in mRNA and in other non-coding RNA species.(63) Since 5hmC in mammalian DNA has remained unconfirmed until 2009,(42,64) it would not be too surprising if this base were also present in RNA, and its detection has so far been ham”