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      The fission yeast MTREC complex targets CUTs and unspliced pre-mRNAs to the nuclear exosome

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          Abstract

          Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. However, the mechanism by which they are recognized and targeted to the exosome is not fully understood. Here we report that the MTREC complex, which has recently been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs, is also the major nuclear exosome targeting complex for CUTs and unspliced pre-mRNAs in Schizosaccharomyces pombe. The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of CUTs.

          Abstract

          The evolutionarily conserved MTREC complex promotes degradation of meiotic mRNAs and regulatory ncRNAs. Here the authors show that MTREC also targets cryptic unstable transcripts and unspliced pre-mRNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process.

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          Most cited references42

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          The Proteomics Identifications (PRIDE) database and associated tools: status in 2013

          The PRoteomics IDEntifications (PRIDE, http://www.ebi.ac.uk/pride) database at the European Bioinformatics Institute is one of the most prominent data repositories of mass spectrometry (MS)-based proteomics data. Here, we summarize recent developments in the PRIDE database and related tools. First, we provide up-to-date statistics in data content, splitting the figures by groups of organisms and species, including peptide and protein identifications, and post-translational modifications. We then describe the tools that are part of the PRIDE submission pipeline, especially the recently developed PRIDE Converter 2 (new submission tool) and PRIDE Inspector (visualization and analysis tool). We also give an update about the integration of PRIDE with other MS proteomics resources in the context of the ProteomeXchange consortium. Finally, we briefly review the quality control efforts that are ongoing at present and outline our future plans.
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            Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase.

            Since detection of an RNA molecule is the major criterion to define transcriptional activity, the fraction of the genome that is expressed is generally considered to parallel the complexity of the transcriptome. We show here that several supposedly silent intergenic regions in the genome of S. cerevisiae are actually transcribed by RNA polymerase II, suggesting that the expressed fraction of the genome is higher than anticipated. Surprisingly, however, RNAs originating from these regions are rapidly degraded by the combined action of the exosome and a new poly(A) polymerase activity that is defined by the Trf4 protein and one of two RNA binding proteins, Air1p or Air2p. We show that such a polyadenylation-assisted degradation mechanism is also responsible for the degradation of several Pol I and Pol III transcripts. Our data strongly support the existence of a posttranscriptional quality control mechanism limiting inappropriate expression of genetic information.
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              RNA degradation by the exosome is promoted by a nuclear polyadenylation complex.

              The exosome complex of 3'-5' exonucleases participates in RNA maturation and quality control and can rapidly degrade RNA-protein complexes in vivo. However, the purified exosome showed weak in vitro activity, indicating that rapid RNA degradation requires activating cofactors. This work identifies a nuclear polyadenylation complex containing a known exosome cofactor, the RNA helicase Mtr4p; a poly(A) polymerase, Trf4p; and a zinc knuckle protein, Air2p. In vitro, the Trf4p/Air2p/Mtr4p polyadenylation complex (TRAMP) showed distributive RNA polyadenylation activity. The presence of the exosome suppressed poly(A) tail addition, while TRAMP stimulated exosome degradation through structured RNA substrates. In vivo analyses showed that TRAMP is required for polyadenylation and degradation of rRNA and snoRNA precursors that are characterized exosome substrates. Poly(A) tails stimulate RNA degradation in bacteria, suggesting that this is their ancestral function. We speculate that this function was maintained in eukaryotic nuclei, while cytoplasmic mRNA poly(A) tails acquired different roles in translation.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                20 May 2015
                2015
                : 6
                : 7050
                Affiliations
                [1 ]Biochemistry Center (BZH), Heidelberg University , Heidelberg 69120, Germany
                [2 ]Faculty of Life and Environmental Sciences, University of Tsukuba , Tsukuba, Ibaraki 305-8577, Japan
                [3 ]Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba , Tsukuba, Ibaraki 305-8577, Japan
                Author notes
                [*]

                These authors contributed equally to this work

                Article
                ncomms8050
                10.1038/ncomms8050
                4455066
                25989903
                83519745-d7e0-4c7f-ad72-ee8992d7e6b8
                Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 19 August 2014
                : 27 March 2015
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