Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome
- Tim R. Mercer1,4,
- Marcel E. Dinger1,4,
- Cameron P. Bracken2,3,
- Gabriel Kolle1,
- Jan M. Szubert2,
- Darren J. Korbie1,
- Marjan E. Askarian-Amiri1,
- Brooke B. Gardiner1,
- Gregory J. Goodall2,3,
- Sean M. Grimmond1 and
- John S. Mattick1,5
- 1 Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia;
- 2 Centre for Cancer Biology, SA Pathology, Adelaide SA 5000, Australia;
- 3 Discipline of Medicine, University of Adelaide, Adelaide SA 5000, Australia
↵4 These authors contributed equally to this work.
Abstract
The complexity of the eukaryotic transcriptome is generated by the interplay of transcription initiation, termination, alternative splicing, and other forms of post-transcriptional modification. It was recently shown that RNA transcripts may also undergo cleavage and secondary 5′ capping. Here, we show that post-transcriptional cleavage of RNA contributes to the diversification of the transcriptome by generating a range of small RNAs and long coding and noncoding RNAs. Using genome-wide histone modification and RNA polymerase II occupancy data, we confirm that the vast majority of intraexonic CAGE tags are derived from post-transcriptional processing. By comparing exonic CAGE tags to tissue-matched PARE data, we show that the cleavage and subsequent secondary capping is regulated in a developmental-stage- and tissue-specific manner. Furthermore, we find evidence of prevalent RNA cleavage in numerous transcriptomic data sets, including SAGE, cDNA, small RNA libraries, and deep-sequenced size-fractionated pools of RNA. These cleavage products include mRNA variants that retain the potential to be translated into shortened functional protein isoforms. We conclude that post-transcriptional RNA cleavage is a key mechanism that expands the functional repertoire and scope for regulatory control of the eukaryotic transcriptome.
Footnotes
↵5 Corresponding author.
E-mail j.mattick{at}imb.uq.edu.au; fax 61-7-3346-2111.
[Supplemental material is available online at http://www.genome.org. The sequence data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSE22627 and GSE24355.]
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.112128.110.
- Received June 25, 2010.
- Accepted September 15, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press