Our Research
The Duchaine lab investigates the complex interplay between mRNA structure and function,
with a particular focus on 3'UTR regulatory elements and their interacting partners.
Our research combines molecular biology and biochemistry, genetics and genomics, proteomics and systems biology.
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We employ multiple model systems including C. elegans, mammalian cells, and mice
to ensure our findings are robust and translatable.
More recently, our lab is translating this knowledge to precision medicine and mRNA-based modalities.
This expansion bridges our foundational research of mRNA biology with cutting-edge therapeutic applications.
Alternative polyadenylation (APA) 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 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.
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Contributions:
mRNA decapping & decay in the functions of miRNAs and development
MicroRNAs 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 C. elegans.
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Contributions:
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.
Contributions:
Our goal is to translate the above bench-level discoveries into innovative mRNA-based therapies. By leveraging our deep understanding of mRNA biology, we are also focusing on developing the next generation of mRNA-based therapeutics.
We are taking an interdisciplinary collaborative approach, working alongside the following laboratories and the mRNA Therapeutics platform to accelerate our RNA discoveries:
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David Juncker - Micro & Nano Bioengineering Lab
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William Muller - Genetically engineered mouse models in cancer research
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Peter Siegel - Research in Cancer Metastasis
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Hamed Najafabadi - Computational and Statistical Genomics Lab
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Amy Pasquinelli - Non-coding RNAs in stress and aging
mRNA therapeutics: bridging basic and translational mRNA research
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.
Contributions:
Thivierge et al. Cell Rep. 2024