Extensive allele‐specific translational regulation in hybrid mice

Molecular Systems Biology

Jingyi Hou¹  Xi Wang¹  Erik McShane²  Henrik Zauber²  Wei Sun¹  Matthias Selbach² 

[1] Laboratory for Functional and Medical Genomics, Berlin Institute for Medical Systems Biology, Berlin, Germany;Laboratory for Proteome Dynamics, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany

关键词: allele‐specific gene expression;    cis‐elements;    translational regulation;   

DOI  :  10.15252/msb.156240

来源: Wiley

【 摘 要 】

Abstract

Translational regulation is mediated through the interaction between diffusible trans-factors and cis-elements residing within mRNA transcripts. In contrast to extensively studied transcriptional regulation, cis-regulation on translation remains underexplored. Using deep sequencing-based transcriptome and polysome profiling, we globally profiled allele-specific translational efficiency for the first time in an F1 hybrid mouse. Out of 7,156 genes with reliable quantification of both alleles, we found 1,008 (14.1%) exhibiting significant allelic divergence in translational efficiency. Systematic analysis of sequence features of the genes with biased allelic translation revealed that local RNA secondary structure surrounding the start codon and proximal out-of-frame upstream AUGs could affect translational efficiency. Finally, we observed that the cis-effect was quantitatively comparable between transcriptional and translational regulation. Such effects in the two regulatory processes were more frequently compensatory, suggesting that the regulation at the two levels could be coordinated in maintaining robustness of protein expression.

Synopsis

Deep sequencing-based transcriptome and polysome profiling reveals extensive allele-specific translational regulation in an F1 hybrid mouse, which enables global analysis of cis-regulatory elements and the coordination between transcriptional and translational regulation.

• Out of 7,156 genes with reliable quantification of both alleles, 1,008 (14.1%) exhibit significant allelic divergence in translational efficiency.
• Systematic analysis of sequence features reveals that local RNA secondary structure surrounding the start codon and proximal out-of-frame upstream AUGs can affect translational efficiency.
• Cis-effects in transcriptional and translational regulatory processes are quantitatively comparable and more frequently compensatory, suggesting coordinated regulation at the two levels.

【 授权许可】

CC BY   
© 2015 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.