Compound Heterozygosity for Y Box Proteins Causes Sterility Due to Loss of Translational Repression

Elizabeth Snyder, Ramani Soundararajan, Manju Sharma, Andrea Dearth, Benjamin Smith, Robert E. Braun

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Article numbere1005690
JournalPLoS genetics
Issue number12
StatePublished - 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research


Dive into the research topics of 'Compound Heterozygosity for Y Box Proteins Causes Sterility Due to Loss of Translational Repression'. Together they form a unique fingerprint.

Cite this