Witold Filipowicz

Epigenetic control of gene expression and post-transcriptional silencing of genes by RNA interference (RNAi) and miRNAs have emerged recently as extraordinarily important and interesting areas of molecular biology. These reactions greatly contribute to the developmental and tissue specificity of gene expression, and also exemplify a key role of hundreds of novel non-coding RNAs in the regulation of gene expression. Our research is focused on mechanistic and regulatory aspects of miRNA function and miRNA metabolism in mammalian cells. miRNAs are ~21-nt RNAs involved in the regulation of development, differentiation, and many other fundamental processes; hundreds of different miRNAs are encoded in the genomes of metazoa. miRNAs generally imperfectly base-pair to the mRNA 3'-UTR and inhibit protein synthesis by either repressing mRNA translation or causing mRNA deadenylation and degradation.

miRNA-mediated regulation is a complex process involving many different proteins and intersecting with other cellular pathways. miRNAs function in the form of miRNPs (also known as miRISC), with Argonaute and GW182 proteins being the most important protein components. Biogenesis of miRNAs is also a complex reaction. It involves two enzymes of the RNase III family, Dicer and Drosha. In addition, many accessory factors regulate miRNA biosynthesis at different steps. miRNAs are generally assumed to have a very long half-life but our recent studies indicate that in some cells, in particular in neurons, miRNAs turn over very fast and that miRNA turnover is a subject of sophisticated regulation.
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