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Dev Cell. 2017 Apr 10;41(1):82-93.e4. doi: 10.1016/j.devcel.2017.03.003. Epub 2017 Mar 30.

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.

Author information

1
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; Laboratories of Neuroembryology, Fondazione Santa Lucia IRCCS, 00143 Rome, Italy.
2
GenoSplice Technology, iPEPS-ICM, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.
3
Fondazione Pasteur Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology Sapienza University of Rome, 00161 Rome, Italy.
4
IUH, Saint-Louis Hospital, 75010 Paris, France.
5
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
6
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; Laboratories of Neuroembryology, Fondazione Santa Lucia IRCCS, 00143 Rome, Italy. Electronic address: claudio.sette@uniroma2.it.

Abstract

Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis.

KEYWORDS:

alternative splicing; germ cell differentiation; intron retention; mRNA stability; spermatogenesis; transcriptome profiling

PMID:
28366282
PMCID:
PMC5392497
DOI:
10.1016/j.devcel.2017.03.003
[Indexed for MEDLINE]
Free PMC Article

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