We have learned a great deal recently about the mechanism and biology of a class of small non-coding RNAs called microRNAs. This remarkable class of RNAs constitute 1 % of the genes in the human genome, and they repress the expression of protein-coding genes. This is achieved in animal specieis primarily by attenation of protein synthesis from messages which contain complementary sequence in their 3' untranslated regions. Although it is difficult to estimate the extent of microRNA regulation, from 4 - 20% of protein-coding genes might be directly controlled by microRNAs. Genetic studies in model organisms support the notion that microRNAs play select roles in cell and organismal biology. We are interested in understanding how microRNAs specifically inhibit their target genes and the biological consequences of this regulation. To this end, we developed a method to detect individual microRNAs in whole Drosophila tissues and embryos by in situ hybridization. We will evaluate the expression patterns of the 78 known Drosophila microRNAs during eye development. The upstream regulatory pathways that regulate microRNA expression in the eye will be evaluated, and correlated to known biological functions of these pathways. We will use microRNA gene mutagenesis to determine if microRNAs are involved in these biological processes. A combination of in silico and molecular genetic approaches will be used to identify and characterize direct targets of microRNA repression, and to investigate the mechanism(s) governing the specificity of microRNA- mediated translational repression. Our goal is to decipher the rules of microRNA regulation regarding target and biological specificity in diverse tissues of the body. The combined effects of microRNAs may affect the expression of many human genes, and misregulation of microRNAs may well underlie complex disease phenomena such as cancer susceptibility and progression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM077581-02S1
Application #
7590087
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Rhoades, Marcus M
Project Start
2006-05-01
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$24,065
Indirect Cost
Name
Northwestern University at Chicago
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Carthew, Richard W; Agbu, Pamela; Giri, Ritika (2017) MicroRNA function in Drosophila melanogaster. Semin Cell Dev Biol 65:29-37
Andress, Arlise; Bei, Yanxia; Fonslow, Bryan R et al. (2016) Spindle-E cycling between nuage and cytoplasm is controlled by Qin and PIWI proteins. J Cell Biol 213:201-11
Cassidy, Justin J; Straughan, Alexander J; Carthew, Richard W (2016) Differential Masking of Natural Genetic Variation by miR-9a in Drosophila. Genetics 202:675-87
Peláez, Nicolás; Gavalda-Miralles, Arnau; Wang, Bao et al. (2015) Dynamics and heterogeneity of a fate determinant during transition towards cell differentiation. Elife 4:
Posadas, Diana M; Carthew, Richard W (2014) MicroRNAs and their roles in developmental canalization. Curr Opin Genet Dev 27:1-6
Boisclair Lachance, Jean-François; Peláez, Nicolás; Cassidy, Justin J et al. (2014) A comparative study of Pointed and Yan expression reveals new complexity to the transcriptional networks downstream of receptor tyrosine kinase signaling. Dev Biol 385:263-78
Cassidy, Justin J; Jha, Aashish R; Posadas, Diana M et al. (2013) miR-9a minimizes the phenotypic impact of genomic diversity by buffering a transcription factor. Cell 155:1556-67
Qi, Jin; Wang, B; Pelaez, N et al. (2013) Drosophila Eye Nuclei Segmentation Based on Graph Cut and Convex Shape Prior. Int Conf Signal Process Proc :670-674
Wu, Pei-Hsuan; Isaji, Mamiko; Carthew, Richard W (2013) Functionally diverse microRNA effector complexes are regulated by extracellular signaling. Mol Cell 52:113-23
Webber, Jemma L; Zhang, Jie; Cote, Lauren et al. (2013) The relationship between long-range chromatin occupancy and polymerization of the Drosophila ETS family transcriptional repressor Yan. Genetics 193:633-49

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