Alterations or deregulated expression of genes involved in RNA splicing are recurrently associated to distinct cancer types and/or are linked to splicing events, which generate the pro-migratory proteins isoforms. Precursor messenger RNA splicing is orchestrated by the spliceosome machinery. All-atom simulations are used to unravel the fundamental mechanism underlying splicing in eukaryotes, to understand the molecular basis of constitutive and alternative splicing, the role of cancer associated mutations, and to develop small molecule inhibitors targeting relevant splicing factor.
This work is supported by the AIRC Investigator Grant and is in collaboration with several experimental groups, Prof. Luca Malcovati San Matteo Hospital and University of Pavia, PV, Dr. J. Valcarcel, Center for Genomic Regulation, Barcelona, Spain, Dr. F. Doria, University of Pavia, Dr. N. Zaffaroni, IRCSS Istituto dei Tumori, Milan, Italy.
Key publications
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. 115, 6584–6589 (2018).
Saltalamacchia, A. et al. Decrypting the Information Exchange Pathways across the Spliceosome Machinery. J. Am. Chem. Soc. 142, 8403–8411 (2020).
Borišek, J. & Magistrato, A. All-Atom Simulations Decrypt the Molecular Terms of RNA Catalysis in the Exon-Ligation Step of the Spliceosome. ACS Catal. 10, 5328–5334 (2020).
Magistrato Lab 