LADE Seminar

Abstract

Complex protein/RNA macromolecular engines, catalyze formation of mature messenger and ribosomal RNAs from their precursors, giving rise to functional RNAs. In this talk I will illustrate how atomic-level simulations have contributed to elucidate: (i) the function of specific protein components of the spliceosome assembly [1,2]; (ii) the chemical details of premature-messenger and premature-ribosomal RNA splicing [3-4], and (iii) the mechanism of spliceosome helicases [5], and (iv) can contribute to refine the cryo-EM structure of complex RNA-based machineries.

1. Casalino, L.; Palermo, G.; Spinello, A.; Rothlisberger, U.; Magistrato, A. All-atom simulations disentangle the functional dynamics underlying gene maturation in the intron lariat spliceosome. Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 6584
2. Saltalamacchia, A.; Casalino, L.; Borišek, J.; Batista, V. S.; Rivalta, I.; Magistrato, A. Decrypting the Information Exchange Pathways across the Spliceosome Machinery. J. Am. Chem. Soc. 2020, 142, 8403
3. Borišek, J.; Magistrato, A. All-Atom Simulations Decrypt the Molecular Terms of RNA Catalysis in the Exon-Ligation Step of the Spliceosome. ACS Catal. 2020, 10, 5328
4. J Aupič, J Borišek, SM Fica, WP Galej, A Magistrato Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome Nature Communications 2023 14 (1), 8482
5. Movilla, S.; Roca, M.; Moliner, V.; Magistrato, A Molecular Basis of RNA-Driven ATP Hydrolysis in DExH-Box Helicases. J. Am. Chem. Soc. 2023, https://doi.org/10.1021/jacs.2c11980"