Abstract
The piwi family genes are crucial for stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. However, their function in mammals remains unexplored. Here we report the cloning of a murine piwi gene (miwi) essential for spermatogenesis. miwi encodes a cytoplasmic protein specifically expressed in spermatocytes and spermatids. miwi(null) mice display spermatogenic arrest at the beginning of the round spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis. Furthermore, mRNAs of ACT (activator of CREM in testis) and CREM target genes are downregulated in miwi(null) testes. Whereas MIWI and CREM do not regulate each other's expression, MIWI complexes with mRNAs of ACT and CREM target genes. Hence, MIWI may control spermiogenesis by regulating the stability of these mRNAs.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Argonaute Proteins
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Chromosome Mapping
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Cloning, Molecular
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Cyclic AMP Response Element Modulator
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Cytoplasm / chemistry
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation
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Infertility, Male / genetics
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LIM Domain Proteins
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Male
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Proteins / genetics*
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Proteins / metabolism*
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RNA, Messenger / genetics
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Repressor Proteins*
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Spermatogenesis / genetics
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Spermatogenesis / physiology*
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Testis / cytology
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Testis / physiology
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Transcription Factors / metabolism
Substances
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Argonaute Proteins
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DNA-Binding Proteins
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Fhl5 protein, mouse
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LIM Domain Proteins
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Piwil1 protein, mouse
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Protein Isoforms
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Proteins
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RNA, Messenger
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Repressor Proteins
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Transcription Factors
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activator of CREM in testis (ACT)
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Cyclic AMP Response Element Modulator