Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage

Bracken, Cameron P., Szubert, Jan M., Mercer, Tim R., Dinger, Marcel E., Thomson, Daniel W., Mattick, John S., Michael, Michael Z. and Goodall, Gregory J. (2011) Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage. Nucleic Acids Research, 39 13: 5658-5668. doi:10.1093/nar/gkr110

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Author Bracken, Cameron P.
Szubert, Jan M.
Mercer, Tim R.
Dinger, Marcel E.
Thomson, Daniel W.
Mattick, John S.
Michael, Michael Z.
Goodall, Gregory J.
Title Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
1362-4962
Publication date 2011-07-01
Sub-type Article (original research)
DOI 10.1093/nar/gkr110
Open Access Status DOI
Volume 39
Issue 13
Start page 5658
End page 5668
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2012
Language eng
Formatted abstract
The Ago2 component of the RNA-induced silencing complex (RISC) is an endonuclease that cleaves mRNAs that base pair with high complementarity to RISC-bound microRNAs. Many examples of such direct cleavage have been identified in plants, but not in vertebrates, despite the conservation of catalytic capacity in vertebrate Ago2. We performed parallel analysis of RNA ends (PAREs), a deep sequencing approach that identifies 5′-phosphorylated, polyadenylated RNAs, to detect potential microRNA-directed mRNA cleavages in mouse embryo and adult tissues. We found that numerous mRNAs are potentially targeted for cleavage by endogenous microRNAs, but at very low levels relative to the mRNA abundance, apart from miR-151-5p-guided cleavage of the N4BP1 mRNA. We also find numerous examples of non-miRNA-directed cleavage, including cleavage of a group of mRNAs within a CA-repeat consensus sequence. The PARE analysis also identified many examples of adenylated small non-coding RNAs, including microRNAs, tRNA processing intermediates and various other small RNAs, consistent with adenylation being part of a widespread proof-reading and/or degradation pathway for small RNAs.
Keyword MicroRNA-directed cleavage
Short interfering RNAs
Messenger-RNA
Saccharomyces-cerevisiae
Ribosomal-RNA
Nuclear-RNA
Human-cells
CA repeats
Arabidopsis
Polyadenylation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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