Towards the mechanism(s) of YB-3 synthesis regulation by YB-1.

Y-box binding proteins are members of the family of proteins containing the evolutionarily conserved cold shock domain. Their cellular functions are quite diverse, including transcription and translation regulation, participation in pre-mRNA splicing, mRNA stabilization and packaging into mRNPs, involvement in DNA repair, and some others. To date, we know little about the plausible functional interchangeability of Y-box binding proteins. Our previous finding was that in YB-1-null HEK293T cells the synthesis of YB-3 is enhanced, thus enabling YB-3 to interact with a larger set of mRNAs and compensate for the YB-1 absence. We suggested the existence of a mechanism of YB-3 synthesis regulation by its paralog, YB-1. Here we demonstrate that YB-1 participates in the translational control and stabilization of YB-3 mRNA through untranslated regions of YB-3 mRNA.

Cold Shock Domain Proteins: Structure and Interaction with Nucleic Acids.

This review summarizes the features of cold shock domain (CSD) proteins in the context of their interactions with nucleic acids and describes similarities and differences in the structure of cold shock proteins of prokaryotes and CSD proteins of eukaryotes with special emphasis on the functions related to the RNA/DNA-binding ability of these proteins. The mechanisms and specificity of their interaction with nucleic acids in relation to the growing complexity of protein domain structure are described, as well as various complexes of the mammalian Y-box binding protein 1 (YB-1) with nucleic acids (filaments, globules, toroids). The role of particular amino acid residues in the binding of nitrogenous bases and the sugar-phosphate backbone of nucleic acids is emphasized. The data on the nucleic acid sequences recognized by the Y-box binding proteins are systematized. Post-translational modifications of YB-1, especially its phosphorylation, affect the recognition of specific sequences in the promoter regions of various groups of genes by YB-1 protein. The data on the interaction of Lin28 protein with let-7 miRNAs are summarized. The features of the domain structure of plant CSD proteins and their effect on the interaction with nucleic acids are discussed.

YB-3 substitutes YB-1 in global mRNA binding.

Y-box binding proteins are DNA- and RNA-binding proteins with an evolutionarily ancient and conserved cold shock domain. The Y-box binding protein 1 (YB-1) is the most studied due to its abundance in somatic cells. YB-1 is involved in a variety of cellular processes, including proliferation, differentiation and stress response. Here, using Ribo-Seq and RIP-Seq we confirm that YB-1 binds a wide range of mRNAs and globally acts as a translation inhibitor. Surprisingly, YBX1 knockout results in only minor alterations in the expression of other genes, mostly caused by changes in RNA abundance. But YB-3 mRNA is an exception: it is better translated in the absence of YB-1, thereby producing an increased amount of YB-3 and thus suggesting that its synthesis is under YB-1 negative control. We have shown that the set of mRNAs bound to YB-3 is strikingly similar to that of YB-1, and that the mRNA-binding by YB-3 is enhanced in the absence of YB-1, resulting in a similar global reduction of translation of bound mRNAs in YB-1-null cells. Thus, YB-3 acts as a substitute for YB-1 in mRNA binding and, probably, in global translational control.