30 March 2023, 11:00
Unraveling the molecular mechanism of pre-mRNA splicing via all atom simulations
30 March 20232023External Faculty SpeakerEMBL Grenoble
AbstractThe spliceosome a complex protein RNA macromolecular machinery removes noncoding introns from precursor messenger RNAs pre mRNAs and ligates coding exons giving rise to protein coding mRNAs and functional non coding 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... AbstractThe spliceosome, a complex protein/RNA macromolecular machinery, removes noncoding introns from precursor messenger RNAs (pre-mRNAs) and ligates coding exons, giving rise to protein coding mRNAs and functional non-coding 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 mechanism of pre-mRNA selection by selected splicing factors, and the impact of cancer associated mutation on pre-mRNA recognition [3]; (iii) the chemical details of pre-mRNA splicing [4,5], and (iv) the mechanism of spliceosome helicases [6]. [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,...
Speaker(s): Alessandra Magistrato, National Research Council-Institute of Material Foundry (CNR-IOM)
Trieste,, Italy
Host: Wojtek Galej - EMBL Grenoble
Place: EMBL Seminar Room
External Faculty Speaker
EMBL Grenoble
Additional information
Abstract
The spliceosome, a complex protein/RNA macromolecular machinery, removes noncoding introns from precursor messenger RNAs (pre-mRNAs) and ligates coding exons, giving rise to protein coding mRNAs and functional non-coding 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 mechanism of pre-mRNA selection by selected splicing factors, and the impact of cancer associated mutation on pre-mRNA recognition [3]; (iii) the chemical details of pre-mRNA splicing [4,5], and (iv) the mechanism of spliceosome helicases [6]. [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.; Saltalamacchia, A.; Galli, A.; Palermo, G.; Molteni, E.; Malcovati, L.; Magistrato, A. Disclosing the Impact of Carcinogenic SF3b Mutations on Pre-mRNA Recognition Via All-Atom Simulations. Biomolecules, 2019, 9, 633. [4] Casalino, L.; Palermo, G.; Rothlisberger, U.; Magistrato A. Who activates the nucleophile in ribozyme catalysis? An answer from the splicing mechanism of group II introns J. Am. Chem. Soc. 2016, 138 (33), 10374 [5] 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 [6] 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
About the speaker
Alessandra Magistrato is research director at of Italian National Research Council (CNR-IOM) c/o International School for Advanced studies, Trieste Italy, where she leads the group computational biology and drug discovery. She obtained her PhD at ETH Zentrum, Zuerich, Switerland, and she was postdoctoral fellow at the University of Pennsylvania, Philadelphia, PA, USA. Her research activity is devoted to the development and application of multi-scale molecular simulations to study protein/RNA machineries, metal ions transporters and cytolytic toxins and in the discovery of drugs targeting them.
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Connection details
Zoom*: https://embl-org.zoom.us/j/96986610968?pwd=d0lEb2NKakx1UVdycFd2TVZIdFgydz09
Meeting ID: 969 8661 0968
Passcode: 480991
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