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
United States
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