Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome.
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.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Tim R
TR
Mercer
Marcel E
ME
Dinger
Cameron P
CP
Bracken
Gabriel
G
Kolle
Jan M
JM
Szubert
Darren J
DJ
Korbie
Marjan E
ME
Askarian-Amiri
Brooke B
BB
Gardiner
Gregory J
GJ
Goodall
Sean M
SM
Grimmond
John S
JS
Mattick
D044127:Epigenesis, Genetic / Q000235:genetics*; D056890:Eukaryota / Q000235:genetics*; D020869:Gene Expression Profiling; D014644:Genetic Variation; D010447:Peptide Hydrolases / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA
D012333:RNA, Messenger; D010447:Peptide Hydrolases