title: An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.
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.
authors.affiliation: 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.
authors.forename: Chiara
authors.initials: C
authors.lastname: Naro
authors.affiliation: GenoSplice Technology, iPEPS-ICM, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Jolly
authors.affiliation: Fondazione Pasteur Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Persio
authors.affiliation: 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.
authors.forename: Pamela
authors.initials: P
authors.lastname: Bielli
authors.affiliation: IUH, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Niclas
authors.initials: N
authors.lastname: Setterblad
authors.affiliation: IUH, Saint-Louis Hospital, 75010 Paris, France.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Alberdi
authors.affiliation: Fondazione Pasteur Cenci Bolognetti, Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology Sapienza University of Rome, 00161 Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Vicini
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Geremia
authors.affiliation: GenoSplice Technology, iPEPS-ICM, Hôpital de la Pitié Salpêtrière, 75013 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: De la Grange
authors.affiliation: 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.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sette
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D063990:Gene Ontology; D007438:Introns / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics*; D008810:Mice, Inbred C57BL; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome / Q000235:genetics
chemical_list: D012333:RNA, Messenger
keywords: alternative splicing; germ cell differentiation; intron retention; mRNA stability; spermatogenesis; transcriptome profiling