Emerging Roles of Ubiquitin-like Proteins in Pre-mRNA Splicing

Ubiquitin-like proteins (UBLs) belong to the protein family whose members share a globular beta-grasp fold structure. The archetypal member, ubiquitin, is known for its function in proteasome-mediated protein degradation. UBLs have been shown to play several crucial roles besides protein turnover, including DNA damage response, cell cycle control, cellular signaling, protein trafficking, and innate immunity activation. In the past few years, accumulating evidence illustrates that four UBLs, namely, ubiquitin, SUMO, Hub1, and Sde2, are involved in eukaryotic pre-mRNA splicing. They modify the spliceosomes and promote splicing by adding new surfaces for intermolecular interactions, thereby refining the outcome of gene expression. In this review article, we highlight recent discoveries with an emphasis on the emerging roles of UBLs in splicing regulation. While members of UBL family are known to play a role in many cellular aspects, recent experimental results suggest emerging roles of UBLs at different steps in pre-mRNA splicing. Spliceosomal components are modified by UBLs, either covalently or non-covalently. Spliceosomal modifications by UBLs are involved in many splicing activities ranging from fostering protein–protein interaction, spliceosome assembly, and activation to controlling splicing fidelity.