U1 snRNP and RNA polymerase II interaction is predominantly mediated by Prp40 rather than U1-70K in yeast

Transcription and splicing are coupled both temporally and physically. A previous cryo-EM structure of the human U1 snRNP and RNA polymerase pol II complex has shown that U1 snRNP uses predominantly the RRM domain of U1-70K to directly interact with the RPB2 subunit of pol II. However, residues on U1-70K involved in the interaction with pol II are not conserved in yeast U1-70K, raising the question whether yeast U1 snRNP interacts with pol II in a similar manner. We found that yeast pol II directly interacts with U1 snRNPs, but U1-70K makes a minimal contribution to this interaction. On the other hand, multiple domains of yeast Prp40 interact with pol II and the removal of the C-terminal domain (CTD) of pol II does not affect this interaction. Although yeast Prp40 is stably associated with U1 snRNP, its human homologs, PRPF40a and PRPF40b, are alternative splicing factors that are not integral components of U1 snRNP. The lack of a stable association between human PRPF40s and U1 snRNP, together with the exposed RRM domain of U1-70K in the absence of PRPF40s, allows U1-70K to serve as the primary mediator of the interaction between U1 snRNP and pol II in humans.