Evidence map›Paper›PMID 30617251›Full record

ArticleCell research2019

A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis.

Marcos Morgan, Yuka Kabayama, Christian Much, Ivayla Ivanova, Monica Di Giacomo, Tatsiana Auchynnikava, Jack Michael Monahan, Dimitrios Michael Vitsios, Lina Vasiliauskaitė, Stefano Comazzetto and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 65 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 4 countries.

Marcos MorganMRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.
Yuka Kabayama *MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.
Christian Much *MRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.ORCID http://orcid.org/0000-0002-1644-8200
Ivayla IvanovaMRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.
Monica Di GiacomoEuropean Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015, Monterotondo, Italy.
Tatsiana AuchynnikavaWellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Jack Michael MonahanEuropean Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK.ORCID http://orcid.org/0000-0002-0635-0015
Dimitrios Michael VitsiosEuropean Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK.ORCID http://orcid.org/0000-0002-8939-5445
Lina VasiliauskaitėMRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK.
Stefano ComazzettoEuropean Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015, Monterotondo, Italy.
Juri RappsilberWellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Robin Campbell AllshireWellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3BF, UK.
Bo Torben PorseBiotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, 2200, Denmark.ORCID http://orcid.org/0000-0001-6043-0844
Anton James EnrightEuropean Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK.
Dónal O'CarrollMRC Centre for Regenerative Medicine, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh, EH16 4UU, UK. donal.ocarroll@ed.ac.uk.
MRC Centre for Regenerative Medicine · GBEuropean Bioinformatics Institute · GBWellcome Centre for Cell Biology · GBEuropean Molecular Biology Laboratory · ITUniversity of Copenhagen · DK

Funding

Role of RNA modifications in spermatogenesis.ZIAES103339 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MORGAN, MARCOS · 2019 to 2025
$10.8M
Wellcome Trust 092076Wellcome Trust 103139/Z/13/ZWellcome Trust 106144Wellcome Trust 200885/Z/16/Z
6 · The paper itself

Abstract

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.

Indexed as

AnimalsFemaleMaleMeiotic Prophase IMiceMice, Inbred C57BLPachytene StageRNA, MessengerRNA Processing, Post-TranscriptionalRNA StabilitySpermatogenesisUDPglucose-Hexose-1-Phosphate UridylyltransferaseRNA, MessengerUDPglucose-Hexose-1-Phosphate Uridylyltransferase

Identifiers

PMID30617251
PMCPMC6420129
OpenAlexW2907757318

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.