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BOR - Papers in Press, published online ahead of print October 11, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.055095
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biolreprod.106.055095v1
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BIOLOGY OF REPRODUCTION 76, 48–54 (2007)
DOI: 10.1095/biolreprod.106.055095
© 2007 by the Society for the Study of Reproduction, Inc.


research-article

In the Absence of the Mouse DNA/RNA-Binding Protein MSY2, Messenger RNA Instability Leads to Spermatogenic Arrest1

Juxiang Yang 3, Carlos R. Morales 4, Sergey Medvedev 5, Richard M. Schultz 5, and Norman B. Hecht 2 3

Center for Research on Reproduction and Women's Health,3 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160 Department of Anatomy and Cell Biology,4 McGill University, Montreal, Quebec, Canada H3A 2B2 Department of Biology,5 University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018

ABSTRACT

MSY2 is a member of the Y-box family of proteins solely expressed in male and female germ cells. In the male, MSY2 serves as a coactivator of transcription by binding to a consensus promoter element present in many germ cell-specific genes. In the nucleus, MSY2 marks specific mRNAs for cytoplasmic storage, stabilization, and suppression of translation. The inactivation of MSY2 by gene targeting leads to spermatogenic arrest and infertility. In testes of mice lacking MSY2, incomplete nuclear condensation is prominent in later-stage spermatids at the time of massive spermatid loss. Because MSY2 interacts with DNA and mRNAs, there are several distinct sites of action, which could be disrupted in mice that lack MSY2, resulting in the arrest of spermatogenesis. To define the molecular cause(s) of the spermatogenic arrest in mice lacking MSY2, transcriptional and posttranscriptional processes were assayed. Transcription, mRNA processing, and mRNA intracellular transport appear normal in the absence of MSY2. However, a redistribution of mRNAs from ribonucleoprotein particles to polysomes and marked decreases were detected for many meiotic and postmeiotic germ cell mRNAs, including the mRNAs encoding the transition proteins and protamines. This suggests that increased mRNA instability is a likely cause of the male infertility in Msy2-null mice.

gene regulation, sperm, spermatid, spermatogenesis, testis


FOOTNOTES

1Supported by NIH grant HD 44449 (to N.B.H. and R.M.S.).

Correspondence: 2 Norman B. Hecht, Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 1310 Biomedical Research Building II/III, 421 Curie Blvd., Philadelphia, PA 19104-6160. FAX: 215 573 5408; e-mail: nhecht{at}mail.med.upenn.edu




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Copyright © 2007 by the Society for the Study of Reproduction.