Marc Fabian obtained his Ph.D. from York University, Toronto, Canada. He completed post-doctoral training with Dr. Nahum Sonenberg (McGill University) where he investigated how microRNAs post-transcriptionally regulate gene expression. Specifically, he focused on investigating how microRNAs inhibit the translation and subsequently promote the degradation of target mRNAs. In 2013, he joined the Lady Davis Institute as an independent investigator. He is an Associate Professor in the Departments of Oncology and Biochemistry, McGill University.
Current Research:
Post-transcriptional control (PTC) programs regulate protein production after a messenger (m) RNA is transcribed from its DNA template. Many PTC programs control protein production by repressing mRNA translation and/or initiating mRNA destabilization, events collectively referred to as ‘silencing’. These programs are in general mediated by RNA binding proteins and ribonucleoprotein complexes that are recruited to specific mRNAs in order to engender silencing. Given their pervasive use, it is not surprising that many human cancers, as well as many other disorders, are associated with defects in gene silencing networks.
The overall theme of my research program is to investigate how microRNAs, RNA binding proteins and ribonucleoprotein complexes translationally repress and/or destabilize target mRNAs in mammalian cells. Ultimately, we wish to use this knowledge to develop new biotechnologies and to identify how aberrant post-transcriptional regulation of gene expression is linked to human disease.
Members of the Fabian lab (left to right): Dr. Marc Fabian, Tamiko Nishimura,
Sahil Sharma, Mona Wu, Hana Fakim.
Selected publications:
(*denotes corresponding authorship)
1. Choquet K, Forget D, Meloche E, Dicaire MJ, Bernard G, Vanderver A, Schiffmann R, Fabian MR, Teichmann M, Coulombe B, Brais B, Kleinman CL. Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. J Biol Chem. 2019 Mar 21. pii: jbc.RA118.006271. doi: 10.1074/jbc.RA118.006271
2. Nishimura T, Fakim H, Brandmann T, Youn JY, Gingras AC, Jinek M, Fabian MR. Human MARF1 is an endoribonuclease that interacts with the DCP1:2 decapping complex and degrades target mRNAs. Nucleic Acids Res. 2018 Dec 14;46(22):12008-12021. doi: 10.1093/nar/gky1011.
3. Duchaine T and Fabian MR*. Mechanistic Insights into MicroRNA-Mediated Gene Silencing. (2018) Cold Spring Harbor Prespect Biol (in press)
4. Brandmann T, Fakim H (co-first author), Padamsi Z, Youn J-Y, Gingras A-C, Fabian MR* and Jinek M*. Molecular architecture of LSM14 interactions involved in the assembly of mRNA silencing complexes. (2018) The EMBO Journal. 37(7):Epub Mar 6
5. Ji-Young Youn, Wade H. Dunham, Seo Jung Hong, James D.R. Knight, Ginny I. Chen, Halil Bagci, Mikhail Bashkurov, Bhavisha Rathod, Graham MacLeod, Simon W. M. Eng, Stéphane Angers, Quaid Morris, Marc Fabian, Jean-François Côté and Anne-Claude Gingras. High-density proximity mapping reveals the subcellular organization of mRNA associated granules and bodies. (2018) Molecular Cell (in press)
6. Nishimura T, and MR Fabian*. 2016. Scanning for a unified model for translational repression by microRNAs. The EMBO Journal. 35(11):1158-9.
7. Nishimura, T., Padamsi, Z., Fakim, H., Milette, S., Dunham, W., Gingras, A-C., and Fabian, M.R.* (2015). The eIF4E binding protein 4E-T is a component of the mRNA decay machinery that bridges the 5´ and 3´ termini of target mRNAs. Cell Reports 11(9):1425-36.
8. Rouya C, Siddiqui N, Morita M, Duchaine TF, Fabian MR*, Sonenberg N. (2014) Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1. RNA 20(9):1398-409.
9. Fabian, M.R.*, Frank, F., Rouya, C., Siddiqui, N., Lai, W.S., Karetnikov, A., Blackshear, P.J., Nagar, B. and Sonenberg, N. (2013) Structural basis for the recruitment of the CCR4-NOT deadenylase complex by Tristetraprolin. Nature Structural & Molecular Biology 20(6):735-9.
10. Fabian, M.R.*and Sonenberg, N. (2012) The mechanics of microRNA-mediated gene silencing: a look under the hood of miRISC. Nature Structural & Molecular Biology 19:1-8.
11. Fabian, M.R., Cieplak, M.K., Frank, F., Morita, M., Green, J., Srikumar, T., Nagar, B., Yamamoto, T., Raught, B., Duchaine, T.F. and Sonenberg, N. (2011) miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nature Structural & Molecular Biology 18(11):1211-7.
12. Fabian, M.R.*, Filipowicz, W. and Sonenberg, N. (2010) Regulation of mRNA translation and stability by MicroRNAs. Annual Review of Biochemistry 79:351-79.
13. Jinek, M., Fabian, M.R., Sonenberg, N. and Doudna J.A. (2010) Structural insights into the human GW182-PABC interactions in microRNA-mediated deadenylation. Nature Structural & Molecular Biology 17:238-240.
14. Fabian, M.R., Mathonnet, G., Sundermeier, T., Mathys, H., Zipprich, J.T., Svitkin, Y., Rivas F., Jinek, M., Wohlschlegel, J., Doudna, J.A., Chen, C.Y., Shyu, A-B., Yates, J.R., Hannon, G.J., Filipowicz, W., Duchaine, T.F. and Sonenberg, N. (2009) Mammalian miRNA RISC recruits CAF-1 and PABP to affect PABP-dependent deadenylation. Molecular Cell 35(6):868-80.
15. Mathonnet, G., Fabian, M.R. (co-first author), Svitkin Y.V., Parsyan, A., Huck, L., Murata, T., Biffo, S., Merrick W.C., Darzynekiewicz, E., Pillai R.S., Duchaine, T.F. and Sonenberg, N. (2007) MicroRNA Inhibition of Translation Initiation In Vitro by Targeting the Cap-Binding Complex eIF4F. Science 317(5845):1764-7.