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Title: Argonaute identity defines the length of mature mammalian microRNAs
Authors: Makeyev, Eugene V.
Juvvuna, Prasanna Kumar
Khandelia, Piyush
Lee, Li Ming
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Juvvuna, P. K., Khandelia, P., Lee, L. M., & Makeyev, E. V. (2012). Argonaute identity defines the length of mature mammalian microRNAs. Nucleic Acids Research, 40(14), 6808-6820.
Series/Report no.: Nucleic acids research
Abstract: MicroRNAs (miRNAs) are 19- to 25-nt-long non-coding RNAs that regulate gene expression by base-pairing with target mRNAs and reducing their stability or translational efficiency. Mammalian miRNAs function in association with four closely related Argonaute proteins, AGO1–4. All four proteins contain the PAZ and the MID domains interacting with the miRNA 30 and 50 termini, respectively, as well as the PIWI domain comprising an mRNA ‘slicing’ activity in the case of AGO2 but not AGO1, AGO3 and AGO4. However, the slicing mode of the miRNA-programmed AGO2 is rarely realized in vivo and the four Argonautes are thought to play largely overlapping roles in the mammalian miRNA pathway. Here, we show that the average length of many miRNAs is diminished during nervous system development as a result of progressive shortening of the miRNA 30 ends. We link this modification with an increase in the fractional abundance of Ago2 in the adult brain and identify a specific structural motif within the PAZ domain that enables efficient trimming of miRNAs associated with this but not the other three Argonautes. Taken together, our data suggest that mammalian Argonautes may define the length and possibly biological activity of mature mammalian miRNAs in a developmentally controlled manner.
DOI: 10.1093/nar/gks293
Rights: © 2012 The Author(s). This paper was published in Nucleic Acids Research and is made available as an electronic reprint (preprint) with permission of The Author(s). The paper can be found at the following official DOI: [].  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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