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From the Section on Molecular Endocrinology, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
| Correspondence to: Chon-Hwa Tsai-Morris, Bldg 49, Rm 6B-03, 49 Convent Dr, MSC 4510, NIH, Bethesda, MD 20892-4510 (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.
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a member of the
Glu-Asp-Ala-Glu (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 posttranscriptional 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/adenosine
triphosphatase activities, GRTH binds to specific mRNAs as an integral
component of ribonuclear protein particles. As a shuttle protein, GRTH
transports target mRNAs from nucleus to the cytoplasm for storage in
chromatoid bodies of spermatids, where they await 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: Testis, spermiogenesis, messenger ribonuclear protein particle, shuttling protein, translation, phosphorylation, chromatoid body, apoptosis, infertility, single-nucleotide polymorphism (SNP), missense mutation
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