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PMID: 22665486 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis.

The Journal of biological chemistry ·Vol. 287 ·No. 30 ·2012-07-20 ·Pages 25173-90

Wu Q, Song R, Ortogero N, Zheng H, Evanoff R, Small CL, Griswold MD, Namekawa SH, Royo H, Turner JM, Yan W

Abstract

DROSHA is a nuclear RNase III enzyme responsible for cleaving primary microRNAs (miRNAs) into precursor miRNAs and thus is essential for the biogenesis of canonical miRNAs. DICER is a cytoplasmic RNase III enzyme that not only cleaves precursor miRNAs to produce mature miRNAs but also dissects naturally formed/synthetic double-stranded RNAs to generate small interfering RNAs (siRNAs). To investigate the role of canonical miRNA and/or endogenous siRNA production in spermatogenesis, we generated Drosha or Dicer conditional knock-out (cKO) mouse lines by inactivating Drosha or Dicer exclusively in spermatogenic cells in postnatal testes using the Cre-loxp strategy. Both Drosha and Dicer cKO males were infertile due to disrupted spermatogenesis characterized by depletion of spermatocytes and spermatids leading to oligoteratozoospermia or azoospermia. The developmental course of spermatogenic disruptions was similar at morphological levels between Drosha and Dicer cKO males, but Drosha cKO testes appeared to be more severe in spermatogenic disruptions than Dicer cKO testes. Microarray analyses revealed transcriptomic differences between Drosha- and Dicer-null pachytene spermatocytes or round spermatids. Although levels of sex-linked mRNAs were mildly elevated, meiotic sex chromosome inactivation appeared to have occurred normally. Our data demonstrate that unlike DICER, which is required for the biogenesis of several small RNA species, DROSHA is essential mainly for the canonical miRNA production, and DROSHA-mediated miRNA production is essential for normal spermatogenesis and male fertility.

MeSH Terms
Animals Azoospermia/enzymology DEAD-box RNA Helicases/genetics,metabolism Fertility/physiology Male Mice Mice, Knockout MicroRNAs/genetics,metabolism Oligospermia/enzymology,genetics Ribonuclease III/genetics,metabolism Spermatids/enzymology Spermatocytes/enzymology Spermatogenesis/physiology Testis/enzymology,growth & development
Chemicals
MicroRNAs Dicer1 protein, mouse Drosha protein, mouse Ribonuclease III DEAD-box RNA Helicases
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Wu Qiuxia
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Song Rui
Ortogero Nicole
Zheng Huili
Evanoff Ryan
Small Chris L
Griswold Michael D
Namekawa Satoshi H
Royo Helene
Turner James M
Yan Wei
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M112.362053
Published
2012-07-20
Epub
2012-00-04
Pages
25173-90
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3408133
Subset
IM
Grants
NICHD NIH HHS · HD050281 · United States
NICHD NIH HHS · HD060858 · United States
NICHD NIH HHS · R01 HD050281 · United States
NIGMS NIH HHS · R01 GM098605 · United States
NICHD NIH HHS · R01 HD060858 · United States
External Links
PubMed source DOI: 10.1074/jbc.M112.362053 PMC Full Text View journal details
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