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      Maternal mRNAs with distinct 3′ UTRs define the temporal pattern of Ccnb1 synthesis during mouse oocyte meiotic maturation

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          Abstract

          In this study, Yang et al. find that the timing of Ccnb1 mRNA translation in mouse oocytes is dependent on the presence of transcripts with different 3′ UTRs. Their results reveal an additional layer of translation control through alternative polyadenylation usage required to fine-tune the timing of meiosis progression.

          Abstract

          The final stages of female gamete maturation occur in the virtual absence of transcription, with gene expression driven by a program of selective unmasking, translation, and degradation of maternal mRNAs. Here we demonstrate that the timing of Ccnb1 mRNA translation in mouse oocytes is dependent on the presence of transcripts with different 3′ untranslated regions (UTRs). This 3′ UTR heterogeneity directs distinct temporal patterns of translational activation or repression. Inclusion or exclusion of cis-acting elements is responsible for these divergent regulations. Our findings reveal an additional layer of translation control through alternative polyadenylation usage required to fine-tune the timing of meiosis progression.

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          Most cited references26

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          Alternative polyadenylation of mRNA precursors

          Alternative polyadenylation (APA) is an RNA-processing mechanism that generates distinct 3′ termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. APA exhibits tissue specificity and is important for
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            Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes.

            Granulosa cells of mammalian Graafian follicles maintain oocytes in meiotic arrest, which prevents their precocious maturation. We show that mouse mural granulosa cells, which line the follicle wall, express natriuretic peptide precursor type C (Nppc) messenger RNA (mRNA), whereas cumulus cells surrounding oocytes express mRNA of the NPPC receptor NPR2, a guanylyl cyclase. NPPC increased cGMP levels in cumulus cells and oocytes and inhibited meiotic resumption in vitro. Meiotic arrest was not sustained in most Graafian follicles of Nppc or Npr2 mutant mice, and meiosis resumed precociously. Oocyte-derived paracrine factors promoted cumulus cell expression of Npr2 mRNA. Therefore, the granulosa cell ligand NPPC and its receptor NPR2 in cumulus cells prevent precocious meiotic maturation, which is critical for maturation and ovulation synchrony and for normal female fertility.
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              Dynamic analyses of alternative polyadenylation from RNA-seq reveal a 3'-UTR landscape across seven tumour types.

              Alternative polyadenylation (APA) is a pervasive mechanism in the regulation of most human genes, and its implication in diseases including cancer is only beginning to be appreciated. Since conventional APA profiling has not been widely adopted, global cancer APA studies are very limited. Here we develop a novel bioinformatics algorithm (DaPars) for the de novo identification of dynamic APAs from standard RNA-seq. When applied to 358 TCGA Pan-Cancer tumour/normal pairs across seven tumour types, DaPars reveals 1,346 genes with recurrent and tumour-specific APAs. Most APA genes (91%) have shorter 3'-untranslated regions (3' UTRs) in tumours that can avoid microRNA-mediated repression, including glutaminase (GLS), a key metabolic enzyme for tumour proliferation. Interestingly, selected APA events add strong prognostic power beyond common clinical and molecular variables, suggesting their potential as novel prognostic biomarkers. Finally, our results implicate CstF64, an essential polyadenylation factor, as a master regulator of 3'-UTR shortening across multiple tumour types.
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                Author and article information

                Journal
                Genes Dev
                Genes Dev
                genesdev
                genesdev
                GAD
                Genes & Development
                Cold Spring Harbor Laboratory Press
                0890-9369
                1549-5477
                1 July 2017
                : 31
                : 13
                : 1302-1307
                Affiliations
                [1 ]State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University (CAU), Beijing 100193, People's Republic of China;
                [2 ]Center for Reproductive Sciences, University of California at San Francisco, San Francisco California 94143, USA;
                [3 ]Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco, California 94143, USA;
                [4 ]Department of Obstetrics and Gynecology and Reproductive Sciences, University of California at San Francisco, San Francisco, California 94143, USA;
                [5 ]Department of Biological Sciences, Inje University, Gimhae 621-749, Republic of Korea
                Author notes
                Corresponding author: contim@ 123456obgyn.ucsf.edu
                Article
                8711660
                10.1101/gad.296871.117
                5580652
                28808066
                0b79d6f2-9df0-4916-afcc-49aea757a9be
                © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press

                This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 17 February 2017
                : 14 July 2017
                Page count
                Pages: 6
                Funding
                Funded by: China Scholarship Council , open-funder-registry 10.13039/501100004543;
                Funded by: Ministry of Education, People's Republic of China , open-funder-registry 10.13039/501100002338;
                Funded by: National Institutes of Health , open-funder-registry 10.13039/100000002;
                Award ID: R01 GM097165
                Award ID: GM116926
                Categories
                Research Communication

                apa,cyclins,meiosis,oocyte,translation
                apa, cyclins, meiosis, oocyte, translation

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