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

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2011

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Bracken, C.
Szubert, J.
Mercer, T.
Dinger, M.
Thomson, D.
Mattick, J.
Michael, M.
Goodall, G.

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Nucleic Acids Research, 2011; 39(13):5658-5668

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Cameron P. Bracken, Jan M. Szubert, Tim R. Mercer, Marcel E. Dinger, Daniel W. Thomson, John S. Mattick, Michael Z. Michael and Gregory J. Goodall

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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.

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© The Author(s) 2011. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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