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Title:
A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis | Cell Research
Description:
Several developmental stages of spermatogenesis are transcriptionally quiescent which presents major challenges associated with the regulation of gene expression. Here we identify that the zygotene to pachytene transition is not only associated with the resumption of transcription but also a wave of programmed mRNA degradation that is essential for meiotic progression. We explored whether terminal uridydyl transferase 4- (TUT4-) or TUT7-mediated 3′ mRNA uridylation contributes to this wave of mRNA degradation during pachynema. Indeed, both TUT4 and TUT7 are expressed throughout most of spermatogenesis, however, loss of either TUT4 or TUT7 does not have any major impact upon spermatogenesis. Combined TUT4 and TUT7 (TUT4/7) deficiency results in embryonic growth defects, while conditional gene targeting revealed an essential role for TUT4/7 in pachytene progression. Loss of TUT4/7 results in the reduction of miRNA, piRNA and mRNA 3′ uridylation. Although this reduction does not greatly alter miRNA or piRNA expression, TUT4/7-mediated uridylation is required for the clearance of many zygotene-expressed transcripts in pachytene cells. We find that TUT4/7-regulated transcripts in pachytene spermatocytes are characterized by having long 3′ UTRs with length-adjusted enrichment for AU-rich elements. We also observed these features in TUT4/7-regulated maternal transcripts whose dosage was recently shown to be essential for sculpting a functional maternal transcriptome and meiosis. Therefore, mRNA 3′ uridylation is a critical determinant of both male and female germline transcriptomes. In conclusion, we have identified a novel requirement for 3′ uridylation-programmed zygotene mRNA clearance in pachytene spermatocytes that is essential for male meiotic progression.
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org/packages/release/bioc/manuals/topgo/man/topgo nature portfolio privacy policy advertising mouse monoclonal anti-α-tubulin project-specific spectral libraries liquid chromatography-ms/ms analysis dutscher scientific nature 480 nature 497 nature 548 nature 543 reprints nature tut7ha-gfp/ha-gfp mice n6-methyladenosine binding protein tut7ha-gfp/ha-gfp embryos small rna libraries generation sequencing libraries canonical au-rich element argonaute-bound small rna tail-seq libraries tut4/7-mediated terminal mono-uridylation rabbit polyclonal anti-smc1a au-rich mrna fate mouse monoclonal anti-ha rabbit polyclonal anti-scp3 bo torben porse rabbit polyclonal anti-tut4 middle hinges anti-orf1 line1 antibody dimitrios michael vitsios m6a-reader yth domain tut4ha-gfp/ha-gfp spermatogenic single-cell dataset49 high-throughput sequencing reads gfp-ythdf2 fusion protein rabbit polyclonal anti-tut7 3′utr-binding rna helicase mouse monoclonal anti-ago2 post-meiotic round spermatids robin campbell allshire & dónal mouse monoclonal anti-γh2ax tut4/7-mediated uridylation underlies canonical au-rich motif 100-nucleotide paired-end mode subsequent oligo-uridylation targets cis-regulatory elements present real-time quantitative pcr permissions
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headline:A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis
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headline:A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis
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name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
type:PostalAddress
type:Organization
name:European Molecular Biology Laboratory (EMBL)
address:
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
type:PostalAddress
type:Organization
name:Ivayla Ivanova
affiliation:
name:University of Edinburgh, 5 Little France Drive
address:
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
type:PostalAddress
type:Organization
name:Monica Di Giacomo
affiliation:
name:European Molecular Biology Laboratory (EMBL)
address:
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
type:PostalAddress
type:Organization
name:Tatsiana Auchynnikava
affiliation:
name:University of Edinburgh
address:
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
name:Jack Michael Monahan
url:http://orcid.org/0000-0002-0635-0015
affiliation:
name:European Bioinformatics Institute
address:
name:European Bioinformatics Institute, Hinxton, UK
type:PostalAddress
type:Organization
name:Dimitrios Michael Vitsios
url:http://orcid.org/0000-0002-8939-5445
affiliation:
name:European Bioinformatics Institute
address:
name:European Bioinformatics Institute, Hinxton, UK
type:PostalAddress
type:Organization
name:Lina VasiliauskaitÄ
affiliation:
name:University of Edinburgh, 5 Little France Drive
address:
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
type:PostalAddress
type:Organization
name:European Molecular Biology Laboratory (EMBL)
address:
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
type:PostalAddress
type:Organization
name:Stefano Comazzetto
affiliation:
name:European Molecular Biology Laboratory (EMBL)
address:
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
type:PostalAddress
type:Organization
name:Juri Rappsilber
affiliation:
name:University of Edinburgh
address:
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
name:Technische Universität Berlin
address:
name:Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
type:PostalAddress
type:Organization
name:Robin Campbell Allshire
affiliation:
name:University of Edinburgh
address:
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
name:Bo Torben Porse
url:http://orcid.org/0000-0001-6043-0844
affiliation:
name:University of Copenhagen
address:
name:Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark
type:PostalAddress
type:Organization
name:University of Copenhagen
address:
name:The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
type:PostalAddress
type:Organization
name:University of Copenhagen
address:
name:Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
type:PostalAddress
type:Organization
name:Anton James Enright
affiliation:
name:European Bioinformatics Institute
address:
name:European Bioinformatics Institute, Hinxton, UK
type:PostalAddress
type:Organization
name:Dónal OâCarroll
affiliation:
name:University of Edinburgh, 5 Little France Drive
address:
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
type:PostalAddress
type:Organization
name:University of Edinburgh
address:
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
name:European Bioinformatics Institute, Hinxton, UK
name:European Bioinformatics Institute, Hinxton, UK
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
name:European Molecular Biology Laboratory (EMBL), Monterotondo, Italy
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
name:Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
name:Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark
name:The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
name:Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
name:European Bioinformatics Institute, Hinxton, UK
name:MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, UK
name:Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
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