Abstract
SUMMARYY-box binding proteins (YBXs) are abundant and conserved nucleic acid-binding proteins that interact with cellular and viral RNAs to modify their stability, localization, and translation. In this review, we summarize the biochemical activities and biological functions of the three human YBX paralogs. Furthermore, we highlight features of RNAs bound by YBXs, including sequence motifs, modifications, and secondary structures. We hypothesize how these features are cooperatively used by YBXs for paralog-specific recognition of RNA targets. Furthermore, we discuss the interactions of YBXs with cellular non-coding RNAs known to be associated with autoimmune diseases. We postulate on how YBXs may interact with these RNAs to maintain cellular homeostasis and prevent aberrant immune activation. Finally, we summarize the roles of YBXs in the life cycles of pathogenic RNA viruses and propose the use of RNA viruses as a valuable tool to dissect unresolved questions in YBX biology.