Education & Training
- B.S. Cornell University-Biology 2001
- M. Phil., Yale University-Molecular Biophysics and Biochemistry 2007
- Ph.D. Yale University, Molecular Biophysics and Biochemistry 2007
Research Interest Summary
My laboratory uses biochemistry, molecular biology, biophysics, and structural biology to discover and dissect the repertoire of interactions between RNA-binding proteins (RBPs) and noncoding regions of mRNA to understand how these interactions govern cellular metabolism. We have established La-related protein 1 (LARP1) as a model to dissect questions addressing: 1) translational regulation, 2) post-translational modifications and their effects on protein structure and function, 3) post-transcriptional modifications of RNA and their roles in RNA metabolism, 3) ribosome biogenesis, 4) mTORC1 signaling, 5) inter-domain interactions, 6) small-molecule targeting of RNA-protein interfaces, and 7) mechanisms underlying transformation in ovarian, liver, kidney, and cervical cancers.
We discovered that LARP1 is a novel bona-fide mRNA cap-binding protein that represses the translation of many transcripts encoding the ribosomal proteins themselves. It does this through its C-terminal conserved region termed the DM15 region. However, this 1019-amino acid protein has at least two other RNA-binding domains (more likely 3) that we expect will cooperate to modulate the RNA-binding activity of LARP1. Therefore, we are interested in dissecting the activities of these domains independently and within the entire protein so that we can begin to study its conformational and functional dynamics. Additionally, we are pursuing the context of the varied functions of LARP1, both in healthy cells and in cancer.
Fonseca, B.D.*, Lahr, R.M., Damgaard, C.K., Alain, T., Berman, A.J.* LARP1 on TOP of Ribosome Production. WIRES RNA. Accepted.
Lahr, R.M., Fonseca, B.D., Ciotti, G.E., Al-Ashtal, H.A., Jia, J-J., Niklaus, M.R., Blagden, S.P., Alain, T., Berman, A.J. LARP1 binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs. (2017). eLife. 6: e24146.
Hopkins, T.G., Mura, M., Al-Ashtal, H.A., Lahr, R.M., Abd-Latip, N., Sweeney, K., Lu, H., Weir, J., El-Bahrawy, M., Steel, J.H., Ghaem-Maghami, S., Aboagye, E.O., Berman, A.J.*, Blagden, S.P*. (2016). The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer. Nuc. Acids Res. 44,1227-46.
Lahr, R.M., Mack, S.M., Héroux, A., Blagden, S.P., Bousquet-Antonelli, C., Deragon, J.M., Berman, A.J. (2015). The LARP1-specific domain DM15 repurposes HEAT-like repeats to directly bind a 5’TOP sequence. Nuc. Acids Res. 43, 8077-88.