title: UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts.
abstract: During transcription, most eukaryotic genes generate multiple alternative cleavage and polyadenylation (APA) sites, leading to the production of transcript isoforms with variable lengths in the 3' untranslated region (3'UTR). In contrast to somatic cells, male germ cells, especially pachytene spermatocytes and round spermatids, express a distinct reservoir of mRNAs with shorter 3'UTRs that are essential for spermatogenesis and male fertility. However, the mechanisms underlying the enrichment of shorter 3'UTR transcripts in the developing male germ cells remain unknown. Here, we report that UPF2-mediated nonsense-mediated mRNA decay (NMD) plays an essential role in male germ cells by eliminating ubiquitous genes-derived, longer 3'UTR transcripts, and that this role is independent of its canonical role in degrading "premature termination codon" (PTC)-containing transcripts in somatic cell lineages. This report provides physiological evidence supporting a noncanonical role of the NMD pathway in achieving global 3'UTR shortening in the male germ cells during spermatogenesis.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Bao
authors.affiliation: Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.|The Bioinformatic Centre, Department of Biology, Faculty of Natural Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Vitting-Seerup
authors.affiliation: Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.|The Bioinformatic Centre, Department of Biology, Faculty of Natural Sciences, University of Copenhagen, Copenhagen, Denmark.|The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Johannes
authors.initials: J
authors.lastname: Waage
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Chong
authors.initials: C
authors.lastname: Tang
authors.affiliation: Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.|The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.|The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bo T
authors.initials: BT
authors.lastname: Porse
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics*; D026723:Polyadenylation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D013087:Spermatids / Q000254:growth & development / Q000378:metabolism; D013090:Spermatocytes / Q000254:growth & development / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C529977:Upf2 protein, mouse