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.
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.
Research topics:
mRNA decapping and decay in the functions of miRNAs and development
miRNAs silence their mRNA targets through a combination of translational repression and deadenylation, decapping, and degradation. The contribution of each mechanism is partially dependent on cellular context. We are studying how various decapping activator proteins regulate Dcp2 function, and how their interactions impact development. Towards this, we use a combination of genome engineering, imaging, biochemistry, and molecular genetics in the nematode C. elegans.
Read our review on decapping activators here.
miRNA-mediated translational repression
The contributions of translational repression versus mRNA decay in miRNA-mediated silencing differ depending on the cell type and organism. We identified the GYF domain-containing protein GYF-1 as the first direct effector of miRNA-mediated translational repression and show demonstrate that inhibition of translation is more important for the function of some, but not all, miRNAs.
Read our latest paper on this topic here.
Mechanisms and functions of nuclear RNAi
Nuclear RNAi interference pathways have wide-ranging impacts on genome organization, chromosome segregation, and protection from viruses and transposable elements. We use the model organism C. elegans to gain biochemical insight into the mechanisms that link Argonautes with heritable epigenetic changes by using a combination of genetics, genomics, proteomics and biochemistry.
Lewis et al. identified a family of nuclear Argonaute-interacting proteins (ENRI-1, ENRI-2, and ENRI-3) that control the strength and target specificity of nuclear RNAi in C. elegans. Lewis et al. 2020.
Alternative polyadenylation of 3′ UTRs
3′ UTRs encode many cis-regulatory structures and sequences that are recognized by trans-acting factors such as miRNAs and RNA-binding proteins. Trans-acting factors can stabilize or destabilize an mRNA transcript through various mechanisms. Alternative polyadenylation (APA) generates mRNA isoforms with different 3′ UTRs lengths, which can impact mRNA stability and translation. We aim to understand the effects of PTEN APA and transcriptome-wide APA on PI3K/Akt signaling and cell function. Thivierge et al. 2018 Tseng et al. 2021
Biogenesis of microRNA polycistrons
miRNAs are key regulators of gene expression. Co-transcriptional processing of primary miRNA transcripts by Drosha is an important step in early miRNA biogenesis. We study the impact of the Microprocessor on pri-miRNA transcription and maturation. We focus on the interplay between host transcripts and mature miRNA maturation and how co-transcriptional processing affects polycistronic miRNA expression.
Donayo et al. identified a mechanism for miR-17∼92 oncogenic function through the disruption of microprocessor with miR-17~92 intermediates. Encumbrance of the microprocessor led to board downregulation of co-expressed polycistronic miRNAs. Donayo et al. 2019.
A complete list of publications can be found here.
Research in the Duchaine lab is supported by:
Duchaine Lab 