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

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.

Gordon Dixon, protamines, and the atypical patterns of gene expression in spermatogenic cells.

Gordon Dixon's pioneering work on the replacement of histones by protamines during spermatogenesis inspired research as recombinant DNA became widely used to analyze gene expression in mammalian spermatogenic cells. The impact of recombinant DNA began immediately with the identification of mouse protamine 1 as a haploid-expressed mRNA, resolving a decades-long controversy whether gene expression in haploid spermatogenic cells distorts transmission of alleles to progeny. Numerous insights into the biology of spermatogenesis followed as the sequences of many mRNAs revealed that the patterns of gene expression in spermatogenic cells are astonishingly different from those in other cells in the mammalian body.

Position-dependent interactions of Y-box protein 2 (YBX2) with mRNA enable mRNA storage in round spermatids by repressing mRNA translation and blocking translation-dependent mRNA decay.

Many mRNAs encoding proteins needed for the construction of the specialized organelles of spermatozoa are stored as translationally repressed, free messenger ribonucleoproteins in round spermatids, to be actively translated in elongating and elongated spermatids. The factors that repress translation in round spermatids, however, have been elusive. Two lines of evidence implicate the highly abundant and well-known translational repressor, Y-box protein 2 (YBX2), as a critical factor: First, protamine 1 (Prm1) and sperm-mitochondria cysteine-rich protein (Smcp) mRNAs are prematurely recruited onto polysomes in Ybx2-knockout mouse round spermatids.

Mechanisms of translational repression of the Smcp mRNA in round spermatids.

The protamine 1 (Prm1) and sperm mitochondria-associated, cysteine-rich protein (Smcp) mRNAs exemplify a widespread pattern of mRNA-specific regulation of mRNA translation in post-meiotic spermatogenic cells, spermatids. Both mRNAs are transcribed and initially stored in free-mRNPs in early spermatids, and translated on polysomes in late spermatids. In this study, we demonstrate that the 5' and 3'-UTRs and the 3' terminus of the Smcp 3'-UTR are required for normal repression of the Smcp mRNA in transgenic mice.

Connecting cis-elements and trans-factors with mechanisms of developmental regulation of mRNA translation in meiotic and haploid mammalian spermatogenic cells.

mRNA-specific regulation of translational activity plays major roles in directing the development of meiotic and haploid spermatogenic cells in mammals. Although many RNA-binding proteins (RBPs) have been implicated in normal translational control and sperm development, little is known about the keystone of the mechanisms: the interactions of RBPs and microRNAs with cis-elements in mRNA targets. The problems in connecting factors and elements with translational control originate in the enormous complexity of post-transcriptional regulation in mammalian cells.