The Duchaine Lab research focuses on RNA-mediated interference (RNAi) pathways, including endogenous RNAi and microRNA-mediated silencing, and their impact on the regulation of gene networks.
Our research program has two main aims:
1) The identification of the functions of small RNAs in development and cancer; and
2) The understanding of the molecular basis of the RNAi phenomena.
The research of our laboratory relies on integrated biochemistry, genetics, and proteomics to explore the RNAi-related phenomena both in C. elegans and in mammalian cells.
Recent progress includes:
♦ the characterization of diverse Pten 3’UTR isoforms and the discovery that alternative polyadenylation sites affect PTEN dosage (Thivierge et al., NAR 2018)
♦ uncovering multiple mechanisms of cooperative miRNA target silencing through a non-canonical miRNA binding site (Flamand et al., NAR 2017)
♦ the discovery that miRNA-mediated silencing in the C.elegans embryo involves the dynamic assembly of effector germ granule and P body-like mRNP complexes on target mRNAs (Wu et al., NAR 2016)
♦ the discovery of a multi-faced mechanism for C. elegans poly(A)-binding proteins (PAB-1 and PAB-2) in miRNA-mediated silencing in embryonic and larval developmental stages (Flamand et al. NAR 2016)
♦ Quantitative assessment of miRISC availability unveils key mechanistic bases for functional competition between co-expressed target RNAs (Mayya & Duchaine NAR 2015)
♦ the discovery that C. elegans Dicer (DCR-1) is proteolytically cleaved to produce an abundant and developmentally regulated C-terminal form (sDCR-1) which modulates multiple RNAi pathways (Sawh & Duchaine Cell Reports 2013).
♦ the dissection of exclusive DCR-1 protein complexes involved in competing RNAi pathways-the ERI endo-RNAi pathway and the exogenous RNAi pathway (Thivierge et al. NSMB 2011).
♦ the discovery of the mechanism of microRNA-mediated silencing in the early embryo, revealing how microRNA families synergize on a subset of binding sites in 3’UTRs to direct potent mRNA deadenylation and silencing (Wu et al. Mol Cell 2010). Part of the group currently examines the impact of these findings in breast cancer, by addressing the implications of interactions between the microRNA complexes on key tumor-suppressor and oncogenic transcripts.