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* To whom correspondence should be addressed. E-mail: morrisch{at}mail.nih.gov.
Male germ cell maturation is governed by the expression of specific protein(s) in a precise temporal sequence during development. GRTH/DDX25, a member of the DEAD-box protein family, is a testis-specific gonadotropin/androgen regulated RNA helicase that is present in germ cells (meiotic spermatocytes and round spermatids) and Leydig cells. GRTH is essential for completion of spermatogenesis as a post-transcriptional regulator of relevant genes during germ cell development. Male mice lacking GRTH are sterile with spermatogenic arrest due to failure of round spermatids to elongate, where striking structural changes and reduction in size of chromatoid bodies are observed. GRTH also plays a central role in preventing germ cell apoptosis. In addition to its inherent helicase unwinding/ATPase activities, GRTH binds to specific mRNAs as an integral component of RNP particles. As a shuttle protein, GRTH transports target mRNAs from nucleus to the cytoplasm for storage in chromatoid bodies of spermatids, awaiting for translation during spermatogenesis. GRTH is also associated with polyribosomes to regulate target gene translation. The finding of a missense mutation associated with male infertility where its expression associates with loss of GRTH phosphorylation supports the relevance of GRTH to human germ cell development. We conclude that the mammalian GRTH/DDX25 is a multifunctional RNA helicase that is an essential regulator of spermatogenesis and is highly relevant for studies of male infertility and contraception.
Key words: Androgen •
Hormone •
Infertility •
Spermatogenesis •
Testis •
Chromatoid body •
RNA helicase •
Single nucleotide polymorphism •
messenger ribonuclear protein particles •
shuttling protein
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