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

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    Rights statement: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. © IBCB, SIBS, CAS 2018

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Original languageEnglish
Number of pages12
JournalCell Research
Early online date7 Jan 2019
DOIs
Publication statusE-pub ahead of print - 7 Jan 2019

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 TUT4 or TUT7-mediated 3ʹ 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 majorly impact spermatogenesis. Combined TUT4 and TUT7 (TUT4/7) deficiency results in embryonic growth defects, however conditional genetics revealed an essential function for TUT4/7 in pachytene progression. Loss of TUT4/7 results in the reduction of 3ʹ miRNA, piRNA and mRNA uridylation. This reduction did not greatly alter miRNA or piRNA expression, whereas TUT4/7-mediated uridylation is required for the clearance of many mRNA zygotene-expressed transcripts in pachytene cells. We find that TUT4/7-regulated transcripts in pachytene spermatocytes are characterized by having long 3ʹ 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 a functional maternal transcriptome and meiosis. Thus 3ʹ mRNA uridylation is a critical determinant of both male and female germline transcriptomes. In conclusion, we identify a novel requirement for 3ʹ uridylation-programmed zygotene mRNA clearance in pachytene spermatocytes that is essential for male meiotic progression.

    Research areas

  • Developmental biology, RNA modification

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