Regulating the Regulators: Mechanisms Controlling Function and Metabolism of microRNAs

Regulating the Regulators: Mechanisms Controlling Function and Metabolism of microRNAs

Air date: Wednesday, April 25, 2012, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local

Category: Wednesday Afternoon Lectures
Description: Micro-Ribonucleic Acids (miRNAs) are a novel class of 20-nucleotide-long regulatory RNAs expressed in eukaryotes. MiRNAs regulate gene expression post-transcriptionally by imperfectly base-pairing to the three prime untranslated region of mRNAs which results in translational repression or mRNA deadenylation and degradation. The number of different miRNAs in human's reaches 1,000, and 50 percent of all human genes are predicted to be subject to miRNA regulation. Although specific functions and target mRNAs have been assigned to only a fraction of identified miRNAs, much evidence exists that miRNAs participate in the regulation of nearly all cellular and developmental processes. Expression of many miRNAs is tissue or development specific and major changes in miRNA expression are observed in human pathologies, including cancer. Clearly, discovery of miRNAs added a new dimension to the complexity and regulation of eukaryotic genomes.

I will discuss current knowledge about the mechanism of miRNA-mediated repression of gene expression, particularly a role of Argonaute and GW182 proteins, and a large multiprotein CCR4-NOT complex which functions downstream and mediates both mRNA deadenylation and translational repression. In addition, biogenesis and turnover of miRNAs, and also the miRNA-mediated repression itself, were recently found to be highly regulated processes involving a plethora of factors with many of them implicated in human pathologies. Finally, I will discuss regulation of miRNA function and turnover in neurons. Our recent work revealed that miRNAs in retinal, hippocampal, and cortical neurons turn over much faster than in non-neuronal cells and that miRNA turnover in neurons may be subject to a complex activity-dependent regulation. Blocking action potentials with tetrodotoxin prevents rapid turnover of miRNAs in neurons. Blocking glutamate receptors likewise prevents decay of many miRNAs in hippocampal and embryonic stem cell derived neurons, while the addition of glutamate accelerates it.

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Author: Dr. Witold Filipowicz, University of Basel
Runtime: 01:00:41
Permanent link: http://videocast.nih.gov/launch.asp?17234

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