Abstract
The Y-box proteins YBX2 and YBX3 bind RNA and DNA and are required for metazoan development and fertility. However, possible functional redundancy between YBX2 and YBX3 has prevented elucidation of their molecular function as RNA masking proteins and identification of their target RNAs. To investigate possible functional redundancy between YBX2 and YBX3, we attempted to construct Ybx2 -/- ;Ybx3 -/- double mutants using a previously reported Ybx2 -/- model and a newly generated global Ybx3 -/- model. Loss of YBX3 resulted in reduced male fertility and defects in spermatid differentiation. However, homozygous double mutants could not be generated as haploinsufficiency of both Ybx2 and Ybx3 caused sterility characterized by extensive defects in spermatid differentiation. RNA sequence analysis of mRNP and polysome occupancy in single and compound Ybx2/3 heterozygotes revealed loss of translational repression almost exclusively in the compound Ybx2/3 heterozygotes. RNAseq analysis also demonstrated that Y-box protein dose-dependent loss of translational regulation was inversely correlated with the presence of a Y box recognition target sequence, suggesting that Y box proteins bind RNA hierarchically to modulate translation in a range of targets.
Highlights
Post-transcriptional control is critical for gene regulation during spermatogenesis as the majority of germ cell transcription ceases many days prior to the completion of differentiation
This study focused on two Y-box proteins, YBX2 and YBX3, expressed in testis and known be important for male fertility
Previous studies in male germ cells link YBX2 and YBX3 proteins to RNA masking, whether they function in translational repression or mRNA stability during spermatogenesis has not been resolved
Summary
Post-transcriptional control is critical for gene regulation during spermatogenesis as the majority of germ cell transcription ceases many days prior to the completion of differentiation. Because the precise differentiation state of a given germ cell can be accurately determined by its association with other germ cells (the stage), defects in temporal post-transcriptional control can be readily detected. This is useful in post-meiotic germ cells, a population comprised of round spermatids that further differentiate to form elongated spermatids. A large number of transcripts required for post-meiotic germ cell differentiation are first transcribed in round spermatids wherein they are sequestered in translationally repressed cytoplasmic messenger ribonucleoprotein (mRNP) particles for up to 7 days [1,2]. While many transcripts have been identified as being under post-transcriptional control, the global and transcript-specific mechanisms underlying this control are not yet elucidated
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