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Down‐regulation of exclusively testis‐expressed microRNA‐469 by gonadotropin‐regulated testicular helicase (GRTH/DDX25) controls male germ cells development
Author(s) -
Dai Lisheng,
TsaiMorris ChonHwa,
Villar Joaquin,
Zhang Jiabao,
Dufau Maria L.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb49
Subject(s) - rna helicase a , biology , messenger rna , gene silencing , spermatid , microrna , microbiology and biotechnology , drosha , rna binding protein , translation (biology) , rna , spermatogenesis , rna interference , gene , genetics , helicase , endocrinology
Gonadotropin‐regulated testicular RNA helicase (GRTH/DDX25), a testis‐specific member of the DEAD‐box family, is an essential post‐transcriptional regulator of spermatogenesis. Failure of expression of Transition protein 2 (TP2) and Protamine 2 (Prm2) proteins (chromatin remodelers, essential for spermatid elongation and completion of spermatogenesis) with preservation of their mRNAs expression was observed in GRTH‐null mice (azoospermic due to failure of spermatids to elongate). These were indentified as target genes for the testis‐specific miR‐469, which is increased in the GRTH‐null mice. Further analysis demonstrated that miR‐469 repressed TP2 and Prm2 protein expression at the translation level with no effect on mRNA expression, through binding to the coding regions of TP2 and Prm2 mRNAs. This indicates miR‐469 silencing function at the translational level. The corresponding primary‐miRNAs (pri‐miRNAs) and the expression levels of Drosha and DGCR8 (both mRNA and protein) were increased significantly in the GRTH‐null mice, suggesting that GRTH regulates the processing pathway of miRNAs at the transcriptional level. Collectively, these studies indicate that GRTH, a multifunctional RNA helicase, acts as a negative regulator of miRNA biogenesis at the transcriptional level by regulating miRNAs expression and consequently their function during spermatogenesis.