DEAH-Box RNA Helicases in Pre-mRNA Splicing

Pre-mRNA splicing is catalyzed by the spliceosome, a multi megadalton protein RNA machinery that undergoes dramatic conformational and compositional rearrangements throughout the splicing cycle, largely driven by eight DExD/H-box RNA helicases. The four helicases participating in the late stages of splicing are all DEAH-box helicases that share structural similarities. Prior genetic, structural, and biochemical studies have revealed much information on the structure, function, mechanism, and regulation of the four DEAH-box splicing helicases. The recent cryo-EM structures of spliceosomal complexes provided a direct visualization of the physiological context of these helicases, offering new insights into their substrates, mechanism of action, and regulation. In eukaryotic cells, pre-mRNA splicing is catalyzed by the spliceosome, a highly dynamic molecular machinery that undergoes dramatic conformational and compositional rearrangements throughout the splicing cycle. These crucial rearrangements are largely driven by eight DExD/H-box RNA helicases. Interestingly, the four helicases participating in the late stages of splicing are all DEAH-box helicases that share structural similarities. This review aims to provide an overview of the structure and function of these DEAH-box helicases, including new information provided by recent cryo-electron microscopy structures of the spliceosomal complexes. In eukaryotic cells, pre-mRNA splicing is catalyzed by the spliceosome, a highly dynamic molecular machinery that undergoes dramatic conformational and compositional rearrangements throughout the splicing cycle. These crucial rearrangements are largely driven by eight DExD/H-box RNA helicases. Interestingly, the four helicases participating in the late stages of splicing are all DEAH-box helicases that share structural similarities. This review aims to provide an overview of the structure and function of these DEAH-box helicases, including new information provided by recent cryo-electron microscopy structures of the spliceosomal complexes.