The control of gene expression by the large class of small (~22nt), noncoding microRNAs has emerged as a new mode of post-transcriptional gene regulation in animal development and disease. The microRNA-induced silencing complex (miRISC) guides microRNAs to the 3 In Aim 1, we will investigate the function of the CSD proteins in the regulation of miR- 1 target expression and binding to the AIN-1 complex. We hypothesize that the CSD proteins recruit the miR-1 target mRNAs, directly or indirectly, to the AIN-1 complex for subsequent target repression.
In Aim 2, we will test the role of the CSD proteins in AIN-1 complex formation and recruitment to the P bodies, the cytoplasmic centers for repression of microRNA target mRNAs. We hypothesize that binding of mRNA substrates by the CSD proteins is a required step for AIN-1 complex formation and targeting to P bodies. Finally, we will test the hypothesis of whether individual CSD proteins form distinct, modular AIN-1 complexes, perhaps as a way to regulate subsets of microRNA targets. We expect that these studies will provide insights into the conserved mechanisms of how microRNA targets are recognized and designated for translational inhibition or degradation.

Public Health Relevance

We have discovered a novel protein complex that we hypothesize functions to regulate the gene targets of microRNAs. MicroRNAs represent a new superfamily of small RNA molecules encoded by all animal genomes. By binding to their target mRNAs, microRNAs prevent the target genes from being translated into proteins. This new paradigm of gene regulation affects a multitude of biological processes in animal development and has been implicated in an increasing number of disease states including cancer and cardiac dysfunction. However, the mechanisms and the cellular machinery required to perform microRNA-mediated target gene regulation remain to be fully characterized. We propose to study our novel AIN-1 protein complex and its critical roles in microRNA target binding and regulation in the body muscles of our model organism, C. elegans.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Molecular Genetics B Study Section (MGB)
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Bender, Michael T
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
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Hong, Sungki; Freeberg, Mallory A; Han, Ting et al. (2017) LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs. Elife 6:
Jin, Meiyan; Fuller, Gregory G; Han, Ting et al. (2017) Glycolytic Enzymes Coalesce in G Bodies under Hypoxic Stress. Cell Rep 20:895-908
Mann, Frederick G; Van Nostrand, Eric L; Friedland, Ari E et al. (2016) Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans. PLoS Genet 12:e1005956
Freeberg, Mallory A; Kim, John K (2016) Mapping the Transcriptome-Wide Landscape of RBP Binding Sites Using gPAR-CLIP-seq: Bioinformatic Analysis. Methods Mol Biol 1361:91-104
Han, Ting; Kim, John K (2016) Mapping the Transcriptome-Wide Landscape of RBP Binding Sites Using gPAR-CLIP-seq: Experimental Procedures. Methods Mol Biol 1361:77-90
Hu, Guowu; McQuiston, Travis; Bernard, Amélie et al. (2015) A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation regulates autophagy. Nat Cell Biol 17:930-942
Alessi, Amelia F; Khivansara, Vishal; Han, Ting et al. (2015) Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1. Proc Natl Acad Sci U S A 112:E7213-22
Chen, Fei; Zhou, Yu; Qi, Yingchuan B et al. (2015) Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development. Genes Dev 29:2377-90
Jin, Meiyan; He, Ding; Backues, Steven K et al. (2014) Transcriptional regulation by Pho23 modulates the frequency of autophagosome formation. Curr Biol 24:1314-1322
Freeberg, Mallory A; Han, Ting; Moresco, James J et al. (2013) Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae. Genome Biol 14:R13

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