The RNA splicing factor Prp45 directs histone H2B ubiquitination through its C-terminal domain

Abstract

While chromatins influence on co-transcriptional splicing is well established, the reciprocal model, that spliceosomal components actively shape chromatin, has lacked mechanistic support. Here we show that the C-terminal intrinsically disordered region (IDR) of the yeast splicing factor Prp45 (mammalian SKIP) promotes histone H2B ubiquitination, a hallmark of active transcription. The Prp45 IDR binds and stabilizes Lge1, the scaffold of the H2B ubiquitin ligase complex, enabling its function with the ubiquitin ligase Bre1. When this interaction is disrupted, Lge1 is degraded by the SUMO-targeted ubiquitin ligase Slx5, Bre1 is mislocalized, H2B ubiquitination is lost, and cells become enlarged. Deleting SLX5 restores Lge1 stability, H2B ubiquitination, and normal cell morphology. Although its sequence diverges across eukaryotes, the IDRs structural properties are conserved, and the disordered regions of Arabidopsis and human SKIP functionally replace the yeast domain. These findings reveal a conserved IDR-mediated mechanism by which a splicing factor directs chromatin modification.