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      microRNAs associated with the different human Argonaute proteins

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          Abstract

          MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3′-untranslated region (3′-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1–3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected.

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          Origins and Mechanisms of miRNAs and siRNAs.

          Richard W. Carthew, Erik J. Sontheimer (2009)
          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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            Gene silencing by microRNAs: contributions of translational repression and mRNA decay.

            Eric Huntzinger, Elisa Izaurralde (2011)
            Despite their widespread roles as regulators of gene expression, important questions remain about target regulation by microRNAs. Animal microRNAs were originally thought to repress target translation, with little or no influence on mRNA abundance, whereas the reverse was thought to be true in plants. Now, however, it is clear that microRNAs can induce mRNA degradation in animals and, conversely, translational repression in plants. Recent studies have made important advances in elucidating the relative contributions of these two different modes of target regulation by microRNAs. They have also shed light on the specific mechanisms of target silencing, which, although it differs fundamentally between plants and animals, shares some common features between the two kingdoms.
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              Argonaute2 is the catalytic engine of mammalian RNAi.

              Jidong Liu, Michelle A Carmell, Fabiola V Rivas … (2004)
              Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi.
              Article 0 comments Cited 714 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nucleic Acids Res
                Journal ID (iso-abbrev): Nucleic Acids Res
                Journal ID (publisher-id): nar
                Journal ID (hwp): nar
                Title: Nucleic Acids Research
                Publisher: Oxford University Press
                ISSN (Print): 0305-1048
                ISSN (Electronic): 1362-4962
                Publication date Collection: October 2012
                Publication date (Print): October 2012
                Publication date (Electronic): 25 July 2012
                Publication date PMC-release: 25 July 2012
                Volume: 40
                Issue: 19
                Pages: 9850-9862
                Affiliations
                1Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany, 2IST Austria (Institute of Science and Technology Austria), Am Campus 1, 3400 Klosterneuburg, Austria, 3Hubrecht Institute for Developmental Biology and Stem Cell Research, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht and 4European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713AV Groningen, The Netherlands
                Author notes
                *To whom correspondence should be addressed. Tel: +49 941 943 2847; Fax: +49 941 943 2936; Email: gunter.meister@ 123456vkl.uni-regensburg.de
                Article
                Publisher ID: gks705
                DOI: 10.1093/nar/gks705
                PMC ID: 3479175
                PubMed ID: 22844086
                SO-VID: a3d125f0-d9a5-4c43-824f-bed13634ec2b
                Copyright © © The Author(s) 2012. Published by Oxford University Press.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 16 May 2012
                Date revision received : 27 June 2012
                Date accepted : 28 June 2012
                Page count
                Pages: 13
                Categories
                Subject: RNA

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

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