6533b7cffe1ef96bd1258499
RESEARCH PRODUCT
All-atom simulations disentangle the functional dynamics underlying gene maturation in the intron lariat spliceosome
Ursula RothlisbergerAngelo SpinelloGiulia PalermoLorenzo CasalinoAlessandra Magistratosubject
Models Molecular0301 basic medicineProtein ConformationSplicingExonMolecular dynamicsRNA; gene maturation; molecular dynamics; spliceosome; splicingModelsRNA Small NuclearRNA PrecursorsMagnesiumPrincipal Component AnalysisMultidisciplinaryChemistrySpliceosomeFungalPhysical SciencesRNA splicingSpliceosomeRNA Splicing1.1 Normal biological development and functioningStatic ElectricityComputational biologyMolecular dynamicsMolecular Dynamics Simulation03 medical and health sciencesMotionsplicingU5 Small NuclearSmall NuclearGeneticUnderpinning researchSchizosaccharomycesGeneticsComputer SimulationGeneRibonucleoprotein U5 Small NuclearModels Geneticgene maturationIntronRNAMolecularRNA FungalRibonucleoproteinIntronsmolecular dynamicsRepressor Proteins030104 developmental biologyGene maturationHelixSpliceosomesRNANucleic Acid ConformationSchizosaccharomyces pombe ProteinsGeneric health relevancespliceosomedescription
The spliceosome (SPL) is a majestic macromolecular machinery composed of five small nuclear RNAs and hundreds of proteins. SPL removes noncoding introns from precursor messenger RNAs (pre-mRNAs) and ligates coding exons, giving rise to functional mRNAs. Building on the first SPL structure solved at near–atomic-level resolution, here we elucidate the functional dynamics of the intron lariat spliceosome (ILS) complex through multi-microsecond-long molecular-dynamics simulations of ∼1,000,000 atoms models. The ILS essential dynamics unveils (i) the leading role of the Spp42 protein, which heads the gene maturation by tuning the motions of distinct SPL components, and (ii) the critical participation of the Cwf19 protein in displacing the intron lariat/ U2 branch helix. These findings provide unprecedented details on the SPL functional dynamics, thus contributing to move a step forward toward a thorough understanding of eukaryotic pre-mRNA splicing.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-01-01 |