biostudies-literatureUnknownEspinosa SNational Institute of General Medical Sciences of the National Institute of HealthNational Institutes of HealthHoward Hughes Medical Institute Gilliam FellowNIGMS NIH HHSthe Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious DiseasesHuman PRPF39 is a homolog of the yeast Prp39 and Prp42 paralogs. We have previously shown that human PRPF39 forms a homodimer that interacts with the CTD of U1C, mirroring the yeast Prp39/Prp42 heterodimer. We demonstrate here that PRPF39 knockdown in HEK293 cells affects many alternative splicing events primarily by reducing the usage of weak 5'ss. Additionally, PRPF39 preferentially binds to a GC-rich RNA, likely at the interface between its NTD and CTD. These data indicate that PRPF39 potentially recruits U1 snRNP to a weak 5' ss, serving as a previously unrecognized alternative splicing factor. We further demonstrate that human TIA1 binds to U1C through its RRM1 and RRM3+Q domains but has no significant binding to PRPF39. Finally, all three human LUC7L isoforms directly interact with URNA (New York, N.Y.)rna.079320.122https://www.ebi.ac.uk/biostudies/studies/S-EPMC9808567biostudies-literatureHuman PRPF39 is an alternative splicing factor recruiting U1 snRNP to weak 5' splice sites.PMC9808567R01 GM129325R35 GM133385T32GM008730F32GM145067R01-GM129325T32 GM008730R35GM133385R35 GM145289R01GM126157R01 GM126157F32 GM145067R35GM145289Li XWagley MEDe Bortoli FRossi JZhao REspinosa SLo HGTaliaferro JMfalseHuman PRPF39 is an alternative splicing factor recruiting U1 snRNP to weak 5' splice sites.Human PRPF39 is a homolog of the yeast Prp39 and Prp42 paralogs. We have previously shown that human PRPF39 forms a homodimer that interacts with the CTD of U1C, mirroring the yeast Prp39/Prp42 heterodimer. We demonstrate here that PRPF39 knockdown in HEK293 cells affects many alternative splicing events primarily by reducing the usage of weak 5'ss. Additionally, PRPF39 preferentially binds to a GC-rich RNA, likely at the interface between its NTD and CTD. These data indicate that PRPF39 potentially recruits U1 snRNP to a weak 5' ss, serving as a previously unrecognized alternative splicing factor. We further demonstrate that human TIA1 binds to U1C through its RRM1 and RRM3+Q domains but has no significant binding to PRPF39. Finally, all three human LUC7L isoforms directly interact with U2022-01-01T00:00:00Z2022 Oct2026-05-28T02:14:39.746Z2025-04-06T19:19:31.388ZS-EPMC98085673631608710.1261/rna.079320.122