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Loss of polyadenylation protein tauCstF-64 causes spermatogenic defects and male infertility.

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, tauCstF-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 tauCstF-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 tauCstF-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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Dass B,Tardif S,Park JY,Tian B,Weitlauf HM,Hess RA,Carnes K,Griswold MD,Small CL,Macdonald CC

doi

10.1073/pnas.0707589104

subject

Has Abstract

pub_date

2007-12-18 00:00:00

pages

20374-9

issue

eissn

0027-8424

issn

1091-6490

pii

0707589104

journal_volume

104

pub_type

杂志文章

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Loss of polyadenylation protein tauCstF-64 causes spermatogenic defects and male infertility.