Journal article
Loss of polyadenylation protein τCstF-64 causes spermatogenic defects and male infertility
Proceedings of the National Academy of Sciences - PNAS, Vol.104(51), pp.20374-20379
12/18/2007
Handle:
https://hdl.handle.net/2376/117560
PMCID: PMC2154438
PMID: 18077340
Abstract
Polyadenylation, the process of eukaryotic mRNA 3′ end formation, is essential for gene expression and cell viability. Polyadenylation of male germ cell mRNAs is unusual, exhibiting increased alternative polyadenylation, decreased AAUAAA polyadenylation signal use, and reduced downstream sequence element dependence. CstF-64, the RNA-binding component of the cleavage stimulation factor (CstF), interacts with pre-mRNAs at sequences downstream of the cleavage site. In mammalian testes, meiotic XY-body formation causes suppression of X-linked CstF-64 expression during pachynema. Consequently, an autosomal paralog, τCstF-64 (gene name
Cstf2t
), is expressed during meiosis and subsequent haploid differentiation. Here we show that targeted disruption of
Cstf2t
in mice causes aberrant spermatogenesis, specifically disrupting meiotic and postmeiotic development, resulting in male infertility resembling oligoasthenoteratozoospermia. Furthermore, the
Cstf2t
mutant phenotype displays variable expressivity such that spermatozoa show a broad range of defects. The overall phenotype is consistent with a requirement for τCstF-64 in spermatogenesis as indicated by the significant changes in expression of thousands of genes in testes of
Cstf2t
−/−
mice as measured by microarray. Our results indicate that, although the infertility in
Cstf2t
−/−
males is due to low sperm count, multiple genes controlling many aspects of germ-cell development depend on τCstF-64 for their normal expression. Finally, these transgenic mice provide a model for the study of polyadenylation in an isolated
in vivo
system and highlight the role of a growing family of testis-expressed autosomal retroposed variants of X-linked genes.
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Details
- Title
- Loss of polyadenylation protein τCstF-64 causes spermatogenic defects and male infertility
- Creators
- Brinda Dass - Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430Steve Tardif - Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430Ji Yeon Park - Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, NJ 07103Bin Tian - Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, NJ 07103Harry M Weitlauf - Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430Rex A Hess - Department of Veterinary Biosciences, University of Illinois, Urbana, IL 61802Kay Carnes - Department of Veterinary Biosciences, University of Illinois, Urbana, IL 61802Michael D Griswold - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164; andChristopher L Small - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164; andClinton C MacDonald - Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.104(51), pp.20374-20379
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- National Academy of Sciences
- Identifiers
- 99900548089801842
- Language
- English
- Resource Type
- Journal article