Y-box proteins combine versatile cold shock domains and arginine-rich motifs (ARMs) for pleiotropic functions in RNA biology.

Abstract

Y-box proteins are single-strand DNA- and RNA-binding proteins distinguished by a conserved cold shock domain (CSD) and a variable C-terminal domain organized into alternating short modules rich in basic or acidic amino acids. A huge literature depicts Y-box proteins as highly abundant, staggeringly versatile proteins that interact with all mRNAs and function in most forms of mRNA-specific regulation. The mechanisms by which Y-box proteins recognize mRNAs are unclear, because their CSDs bind a jumble of diverse elements, and the basic modules in the C-terminal domain are considered to bind nonspecifically to phosphates in the RNA backbone. A survey of vertebrate Y-box proteins clarifies the confusing names for Y-box proteins, their domains, and RNA-binding motifs, and identifies several novel conserved sequences: first, the CSD is flanked by linkers that extend its binding surface or regulate co-operative binding of the CSD and N-terminal and C-terminal domains to proteins and RNA. Second, the basic modules in the C-terminal domain are bona fide arginine-rich motifs (ARMs), because arginine is the predominant amino acid and comprises 99% of basic residues. Third, conserved differences in AA (amino acid) sequences between isoforms probably affect RNA-binding specificity. C-terminal ARMs connect with many studies, demonstrating that ARMs avidly bind sites containing specific RNA structures. ARMs crystallize insights into the under-appreciated contributions of the C-terminal domain to site-specific binding by Y-box proteins and difficulties in identifying site-specific binding by the C-terminal domain. Validated structural biology techniques are available to elucidate the mechanisms by which YBXprot (Y-box element-binding protein) CSDs and ARMs identify targets.