title: Loss of the nuclear receptor corepressor SLIRP compromises male fertility.
abstract: Nuclear receptors (NRs) and their coregulators play fundamental roles in initiating and directing gene expression influencing mammalian reproduction, development and metabolism. SRA stem Loop Interacting RNA-binding Protein (SLIRP) is a Steroid receptor RNA Activator (SRA) RNA-binding protein that is a potent repressor of NR activity. SLIRP is present in complexes associated with NR target genes in the nucleus; however, it is also abundant in mitochondria where it affects mitochondrial mRNA transcription and energy turnover. In further characterisation studies, we observed SLIRP protein in the testis where its localization pattern changes from mitochondrial in diploid cells to peri-acrosomal and the tail in mature sperm. To investigate the in vivo effects of SLIRP, we generated a SLIRP knockout (KO) mouse. This animal is viable, but sub-fertile. Specifically, when homozygous KO males are crossed with wild type (WT) females the resultant average litter size is reduced by approximately one third compared with those produced by WT males and females. Further, SLIRP KO mice produced significantly fewer progressively motile sperm than WT animals. Electron microscopy identified disruption of the mid-piece/annulus junction in homozygous KO sperm and altered mitochondrial morphology. In sum, our data implicates SLIRP in regulating male fertility, wherein its loss results in asthenozoospermia associated with compromised sperm structure and mitochondrial morphology.
authors: Laboratory for Cancer Medicine, The University of Western Australia Centre for Medical Research, Western Australian Institute for Medical Research, Perth, Australia.
authors: Shane M
authors: SM
authors: Colley
authors: Larissa
authors: L
authors: Wintle
authors: Richelle
authors: R
authors: Searles
authors: Victoria
authors: V
authors: Russell
authors: Renee C
authors: RC
authors: Firman
authors: Stephanie
authors: S
authors: Smith
authors: Kathleen
authors: K
authors: Deboer
authors: D Jo
authors: DJ
authors: Merriner
authors: Ben
authors: B
authors: Genevieve
authors: Jacqueline M
authors: JM
authors: Bentel
authors: Bronwyn G A
authors: BG
authors: Stuckey
authors: Michael R
authors: MR
authors: Phillips
authors: Leigh W
authors: LW
authors: Simmons
authors: David M
authors: DM
authors: de Kretser
authors: Moira K
authors: MK
authors: O'Bryan
authors: Peter J
authors: PJ
authors: Leedman
mesh_terms: D000818:Animals; D053627:Asthenozoospermia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006720:Homozygote; D008098:Litter Size; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013094:Spermatozoa / Q000378:metabolism* / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C544451:SLIRP protein, mouse; C029305:mitochondrial messenger RNA
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