A family of short RNA species ranging from in size 20 to 30 nucleotides has been identified and designated as small RNAs. Small RNAs are gene products and derived from double-stranded RNA (dsRNA) precursors that are processed by the ribonuclease type III enzyme Dicer. An increasing body of evidence has shown that these small noncoding RNAs play important roles in the regulation of gene expression including mRNA degradation, transcriptional repression, and chromatin modification. Science named this discovery as 2002's Breakthrough of the Year! No effort has been made to clone small RNAs expressed during mouse testicular development and spermatogenesis so far. Our hypothesis is that the male germ cells express numerous small RNAs in a spatial and temporal manner; many of these small RNAs are testes-specific and function as translational regulators and chromatin modifiers by regulating their target gene expression, or direct interaction, with heterochromatin during spermatogenesis. As an initial effort to test our hypothesis, we propose to perform the following studies: (1) cloning and sequencing of small RNAs expressed during testicular development and spermatogenesis; (2) determination of spatiotemporal expression profiles of the testes-specific small RNAs; (3) establishing of a Web-based testes-expressed small RNA database. The discovery of small RNAs expressed during development and involved in gene regulation opens a brand new avenue toward our better understanding of the mechanisms of gene regulation. For decades, reproductive biologists have been trying to dissect the regulatory mechanisms involved in gene expression regulation during spermatogenesis. The proposed work will identify most, if not all, small RNA species expressed during germ cell development, thus providing important preliminary data for the entire research community to further dissect molecular mechanisms that govern gene expression during spermatogenesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD048855-02
Application #
6984096
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Rankin, Tracy L
Project Start
2004-12-01
Project End
2007-11-30
Budget Start
2005-12-01
Budget End
2007-11-30
Support Year
2
Fiscal Year
2006
Total Cost
$70,796
Indirect Cost
Name
University of Nevada Reno
Department
Physiology
Type
Schools of Medicine
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557
Ro, Seungil; Ma, Hsiu-Yen; Park, Chanjae et al. (2013) The mitochondrial genome encodes abundant small noncoding RNAs. Cell Res 23:759-74
Ortogero, Nicole; Hennig, Grant W; Langille, Chad et al. (2013) Computer-assisted annotation of murine Sertoli cell small RNA transcriptome. Biol Reprod 88:3
Idler, R Keegan; Hennig, Grant W; Yan, Wei (2012) Bioinformatic identification of novel elements potentially involved in messenger RNA fate control during spermatogenesis. Biol Reprod 87:138
Idler, R Keegan; Yan, Wei (2012) Control of messenger RNA fate by RNA-binding proteins: an emphasis on mammalian spermatogenesis. J Androl 33:309-37
Park, Chanjae; Yan, Wei; Ward, Sean M et al. (2011) MicroRNAs dynamically remodel gastrointestinal smooth muscle cells. PLoS One 6:e18628
Park, Chanjae; Hennig, Grant W; Sanders, Kenton M et al. (2011) Serum response factor-dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes. Gastroenterology 141:164-75
Ro, Seungil; Yan, Wei (2010) Detection and quantitative analysis of small RNAs by PCR. Methods Mol Biol 629:295-305
Song, Rui; Ro, Seungil; Yan, Wei (2010) In situ hybridization detection of microRNAs. Methods Mol Biol 629:287-94
Ro, Seungil; Yan, Wei (2010) Small RNA cloning. Methods Mol Biol 629:273-85
Yan, Wei; Si, Yue; Slaymaker, Sarah et al. (2010) Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor essential for spermiogenesis and male fertility. J Biol Chem 285:31418-26

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