title: Extensive allele-specific translational regulation in hybrid mice.
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.
authors.affiliation: Laboratory for Functional and Medical Genomics, Berlin Institute for Medical Systems Biology, Berlin, Germany.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hou
authors.affiliation: Laboratory for Functional and Medical Genomics, Berlin Institute for Medical Systems Biology, Berlin, Germany.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory for Proteome Dynamics, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: McShane
authors.affiliation: Laboratory for Proteome Dynamics, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zauber
authors.affiliation: Laboratory for Functional and Medical Genomics, Berlin Institute for Medical Systems Biology, Berlin, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Laboratory for Proteome Dynamics, Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Selbach
authors.affiliation: Laboratory for Functional and Medical Genomics, Berlin Institute for Medical Systems Biology, Berlin, Germany wei.chen@mdc-berlin.de.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002678:Chimera / Q000235:genetics*; D005347:Fibroblasts; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: allele‐specific gene expression; cis‐elements; translational regulation