biostudies-literatureQiu RNIGMS NIH HHS1289-1301https://www.ebi.ac.uk/biostudies/studies/S-EPMC7353152biostudies-literatureUnknown31(12)The multi-component cytoplasmic dynein transports cellular cargoes with the help of another multi-component complex dynactin, but we do not know enough about factors that may affect the assembly and functions of these proteins. From a genetic screen for mutations affecting early-endosome distribution in <i>Aspergillus nidulans</i>, we identified the <i>prp40A</i>^L438* mutation in Prp40A, a homologue of Prp40, an essential RNA-splicing factor in the budding yeast. Prp40A is not essential for splicing, although it associates with the nuclear splicing machinery. The <i>prp40A</i>^L438* mutant is much healthier than the ∆<i>prp40A</i> mutant, but both mutants exhibit similar defects in dynein-mediated early-endosome transport and nuclear distribution. In the <i>prp40A</i>^L438* mutant, the frequency but not the speed of dynein-mediated early-endosome transport is decreased, which correlates with a decrease in the microtubule plus-end accumulations of dynein and dynactin. Within the dynactin complex, the actin-related protein Arp1 forms a mini-filament. In a pull-down assay, the amount of Arp1 pulled down with its pointed-end protein Arp11 is lowered in the <i>prp40A</i>^L438* mutant. In addition, we found from published interactome data that a mammalian Prp40 homologue PRPF40A interacts with Arp1. Thus, Prp40 homologues may regulate the assembly or function of dynein-dynactin and their mechanisms deserve to be further studied.Molecular biology of the cellThe splicing-factor Prp40 affects dynein-dynactin function in <i>Aspergillus nidulans</i>.PMC7353152R01 GM121850Zhang JQiu RXiang XfalseThe splicing-factor Prp40 affects dynein-dynactin function in <i>Aspergillus nidulans</i>.The multi-component cytoplasmic dynein transports cellular cargoes with the help of another multi-component complex dynactin, but we do not know enough about factors that may affect the assembly and functions of these proteins. From a genetic screen for mutations affecting early-endosome distribution in <i>Aspergillus nidulans</i>, we identified the <i>prp40A</i>^L438* mutation in Prp40A, a homologue of Prp40, an essential RNA-splicing factor in the budding yeast. Prp40A is not essential for splicing, although it associates with the nuclear splicing machinery. The <i>prp40A</i>^L438* mutant is much healthier than the ∆<i>prp40A</i> mutant, but both mutants exhibit similar defects in dynein-mediated early-endosome transport and nuclear distribution. In the <i>prp40A</i>^L438* mutant, the frequency but not the speed of dynein-mediated early-endosome transport is decreased, which correlates with a decrease in the microtubule plus-end accumulations of dynein and dynactin. Within the dynactin complex, the actin-related protein Arp1 forms a mini-filament. In a pull-down assay, the amount of Arp1 pulled down with its pointed-end protein Arp11 is lowered in the <i>prp40A</i>^L438* mutant. In addition, we found from published interactome data that a mammalian Prp40 homologue PRPF40A interacts with Arp1. Thus, Prp40 homologues may regulate the assembly or function of dynein-dynactin and their mechanisms deserve to be further studied.2020-01-01T00:00:00Z2020 Jun2025-04-04T08:19:51.933Z2025-04-04T08:19:51.933ZS-EPMC73531523226720710.1091/mbc.E20-03-0166