Journal article
The RNase III Enzyme DROSHA Is Essential for MicroRNA Production and Spermatogenesis
The Journal of biological chemistry, Vol.287(30), pp.25173-25190
07/20/2012
Handle:
https://hdl.handle.net/2376/110656
PMCID: PMC3408133
PMID: 22665486
Abstract
Background:
miRNA biogenesis requires two RNase III enzymes, DROSHA and DICER.
Results:
Lack of DROSHA in the male germ line leads to deficiency in miRNA production and male infertility.
Conclusion:
DROSHA and DICER have both common and unique functions in male germ cell development.
Significance:
This study reveals an essential role of DROSHA, DICER, and DROSHA-/DICER-dependent small noncoding RNAs spermatogenesis.
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.
Metrics
11 Record Views
Details
- Title
- The RNase III Enzyme DROSHA Is Essential for MicroRNA Production and Spermatogenesis
- Creators
- Qiuxia Wu - From theRui Song - From theNicole Ortogero - From theHuili Zheng - From theRyan Evanoff - theChris L Small - theMichael D Griswold - theSatoshi H Namekawa - theHelene Royo - theJames M Turner - theWei Yan - From the
- Publication Details
- The Journal of biological chemistry, Vol.287(30), pp.25173-25190
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- HD050281; HD060858 / National Institutes of Health
- Identifiers
- 99900547201001842
- Language
- English
- Resource Type
- Journal article