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Region Hovedstaden - en del af Københavns Universitetshospital
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A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis

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  • Marcos Morgan
  • Yuka Kabayama
  • Christian Much
  • Ivayla Ivanova
  • Monica Di Giacomo
  • Tatsiana Auchynnikava
  • Jack Michael Monahan
  • Dimitrios Michael Vitsios
  • Lina Vasiliauskaitė
  • Stefano Comazzetto
  • Juri Rappsilber
  • Robin Campbell Allshire
  • Bo Torben Porse
  • Anton James Enright
  • Dónal O'Carroll
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftExperimental Cell Research
Vol/bind29
Udgave nummer3
Sider (fra-til)221-232
Antal sider12
ISSN0014-4827
DOI
StatusUdgivet - 1 mar. 2019

ID: 56211894