Small Regulatory RNA
MicroRNAs (miRNAs), a large class of short non-coding RNAs found in many plants and animals, often act to inhibit gene expression post-transcriptionally. Approximately 3% of all known human genes encode miRNAs. Important functions for miRNAs in animal development and physiology are emerging. A number of miRNAs have been directly implicated in human disease. We have generated loss-of-function mutations in almost all of the 112 known miRNA genes in the nematode Caenorhabditis elegans. This collection provides the only comprehensive resource for the genetic analysis of individual miRNAs to date. Our main goal is to understand the genetic networks underlying miRNA-dependent control of development.
We are also studying other short RNA (sRNA) species, their biology and mechanism of action. For example, we recently identified the piRNAs of C elegans. piRNAs are required for germline development and maintenance in worms, flies and mammals. Neither the biogenesis nor the mechanism of action is understood for this class of small RNAs. We are using genetic screens, biochemical and molecular biology approaches to address basic questions about sRNA biology. Of particular interest is how small RNA regulatory networks interact with the genome and the environment.
In addition, we have developed tools for the analysis of miRNA expression in human disease and have discovered miRNAs that have potential as molecular markers for diagnosis and prognosis.
- Lehrbach N, Armisen J, Lightfoot H, Murfitt K, Bugaut A, Balasubramanian S, Miska E A (2009) LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans. Nature Struct Mol Biology, 16, 1016-1022
- Lehrbach N J, Castro C, Murfitt K J, Abreu-Goodger C, Griffin J L and Miska E A (2012) Post-developmental microRNA expression is required for normal physiology, and regulates aging in parallel to insulin/IGF-1 signaling in C. elegans. RNA,18, 2220 - 2235
- Ashe A, Sapetschnig A, Weick EM, Mitchell J, Bagijn M P, Cording A C, Doebley A L, Goldstein L D, Lehrbach N J, Le Pen J, Pintacuda G, Sakaguchi A, Sarkies P, Ahmed S and Miska E A (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell, 150, 88 - 99