Abstract
The protein Prp45 has well-characterized roles in RNA splicing. Although it has also been implicated in transcription elongation in metazoans, the mechanism for a role for Prp45 outside of splicing is unclear. Here, we combine genetic, proteomic, and biochemical approaches to show that the C-terminal region of the protein functionally and physically interacts with proteins involved in histone H2B ubiquitination, a mark of transcription elongation. Specifically, we find that Prp45 interacts with Lge1, the scaffold protein that is essential for the activity of the H2B ubiquitin ligase complex, through both Lge1's coiled-coil and intrinsically disordered domains, and these interactions are necessary to stabilize Lge1. In the absence of the Prp45 C-terminus interactions, the cells show a severe loss in H2B ubiquitination, a "Large" (Lge1) phenotype, and defective splicing of a subset of H2B-ubiquitination-dependent intron-containing transcripts. Together these data demonstrate an extra-spliceosomal role for the C-terminus of Prp45 in chromatin modification, RNA splicing, and proper cellular function.