We are driven by questions that underlie how human messenger RNAs (mRNAs) and the ribosome are regulated to determine when, where, and how much of a protein to synthesize. Dysregulated protein synthesis is a universal feature of cancer and a hallmark of viral infections. Yet, molecular models for how translation is controlled remain poorly defined. We therefore examine the interplay between the mRNA, the translation initiation machinery, and the vast repertoire of human and viral proteins that define the efficiency of protein synthesis in space and time. The fundamental discoveries uncovered by our research group will enhance understanding of how cells function and reveal how control goes awry in human diseases, such as cancers and viral infections.
eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining. Lapointe CP, Grosely R, Sokabe M, Alvarado C, Wang J, Montabana E, Villa N, Shin B-S, Dever TE, Fraser CS, Fernández IS, and Puglisi JD. 2022. eIF5B and eIF1A. Nature. 607, 185-190.
Dynamic competition between SARS-CoV-2 NSP1 and mRNA on the human ribosome inhibits translation initiation. Lapointe CP, Grosely R, Johnson AG, Wang J, Fernández IS, and Puglisi JD. 2021. Proceedings of the National Academy of Sciences, USA. 118 (6), e2017715118.