Loss of the Nuclear Receptor Corepressor SLIRP Compromises Male Fertility

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 i...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	PloS one Ročník 8; číslo 8; s. e70700
Hlavní autori:	Colley, Shane M., Wintle, Larissa, Searles, Richelle, Russell, Victoria, Firman, Renee C., Smith, Stephanie, DeBoer, Kathleen, Merriner, D. Jo, Genevieve, Ben, Bentel, Jacqueline M., Stuckey, Bronwyn G. A., Phillips, Michael R., Simmons, Leigh W., de Kretser, David M., O'Bryan, Moira K., Leedman, Peter J.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 15.08.2013 Public Library of Science (PLoS)
Predmet:	Animals Asthenozoospermia - genetics Asthenozoospermia - metabolism Asthenozoospermia - pathology Biology Cancer Cell Nucleus - genetics Cell Nucleus - metabolism Developmental biology Electron microscopy Evolutionary biology Female Females Fertility Gene expression Gene Expression Regulation Genes Genetic aspects Homozygote Hormones In vivo methods and tests Infertility Laboratories Litter Size Localization Male Males Medical research Medicine Metabolism Mice Mice, Knockout Mitochondria Mitochondria - genetics Mitochondria - metabolism Mitochondria - ultrastructure Morphology Motility mRNA turnover Nuclear receptors Nuclei Pharmacology Physiological aspects Protein binding Protein turnover Proteins Receptors Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism Ribonucleic acid RNA RNA, Messenger - genetics RNA, Messenger - metabolism RNA-binding protein RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Rodents Signal Transduction Sperm Spermatogenesis Spermatozoa - metabolism Spermatozoa - ultrastructure Testis - metabolism Testis - pathology Transcription Transcription, Genetic Australia Perth Western Australia Australia
ISSN:	1932-6203, 1932-6203
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist. MO and PL are joint senior authors on this work. Conceived and designed the experiments: SC DdK MO PL. Performed the experiments: SC LW RS VR RF SS KdB DJM BG JB. Analyzed the data: SC LW RS DJM BS MP LS DdK MO PL. Contributed reagents/materials/analysis tools: RF LS BG BS LS DdK MO PL. Wrote the paper: SC JB BS DdK MO PL.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0070700