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

Abstract

SUMMARYMany 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. Second, mutations in 3 0 untranslated region (3 0 UTR) cis-elements that abrogate YBX2 binding activate translation of Prm1 and Smcp mRNAs in round spermatids of transgenic mice. The abundance of YBX2 and its affinity for variable sequences, however, raise questions of how YBX2 targets specific mRNAs for repression. Mutations to the Prm1 and Smcp mRNAs in transgenic mice reveal that strong repression in round spermatids requires YBX2 binding sites located near the 3 0 ends of their 3 0 UTRs as locating the same sites in upstream positions produce negligible repression. This location-dependence implies that the assembly of repressive complexes is nucleated by adjacent cis-elements that enable cooperative interactions of YBX2 with co-factors. The available data suggest that, in vertebrates, YBX2 has the important role of coordinating the storage of translationally repressed mRNAs in round spermatids by inhibiting translational activity and the degradation of transcripts via translation-dependent deadenylation. These insights should facilitiate future experiments designed to unravel how YBX2 targets mRNAs for repression in round spermatids and how mutations in the YBX2 gene cause infertility in humans.

A genome-wide single nucleotide polymorphism and copy number variation analysis for number of piglets born alive

“…The ZMYND15 gene is primordial for sperm production and male fertility [66]. The YBX2 gene codifies a protein required for mammal development and fertility because knockout mice for this gene presented disruption of spermatogenesis and oogenesis [67–69]. The TMEM95 gene codifies a protein located at the surface of spermatozoa and deficiency of TMEM95 severely compromises male reproductive performance, resulting in subfertility in cattle [70].…”

Mouse TMCO5 is localized to the manchette microtubules involved in vesicle transfer in the elongating spermatids

“…Therefore, the transcripts, such as Tmco5, which are translated after elongating spermatids for spermiogenesis, are transcribed in the round spermatids and are stored as translationally repressed state until use. With regards to this regulatory mechanism, RNA-binding proteins and corresponding cis-elements, mainly located in the 3' untranslated region, are known to be involved [32]. For example, the mRNA for Protamin 2 is transcribed at step 7.…”

RNA-Binding Proteins in the Regulation of Adipogenesis and Adipose Function

“…These studies suggested that YBX1 and YBX2 are key players in modulating BAT adipogenesis and thermogenesis by affecting RNA stability. Regarding one of the well-characterized functions of YBXs is regulating translation [ 91 , 92 ], and whether these proteins are involved in the translation of target RNA is not yet answered. In addition, the role of Ybx3 in BAT is little known.…”