Ribosome-Mediated Specificity in Hox mRNA Translation and Vertebrate Tissue Patterning

SummaryHistorically, the ribosome has been viewed as a complex ribozyme with constitutive rather than regulatory capacity in mRNA translation. Here we identify mutations of the Ribosomal Protein L38 (Rpl38) gene in mice exhibiting surprising tissue-specific patterning defects, including pronounced homeotic transformations of the axial skeleton. In Rpl38 mutant embryos, global protein synthesis is unchanged; however the translation of a select subset of Homeobox mRNAs is perturbed. Our data reveal that RPL38 facilitates 80S complex formation on these mRNAs as a regulatory component of the ribosome to confer transcript-specific translational control. We further show that Rpl38 expression is markedly enriched in regions of the embryo where loss-of-function phenotypes occur. Unexpectedly, a ribosomal protein (RP) expression screen reveals dynamic regulation of individual RPs within the vertebrate embryo. Collectively, these findings suggest that RP activity may be highly regulated to impart a new layer of specificity in the control of gene expression and mammalian development.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (7838 K)

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (318 K)Download as PowerPoint slideHighlights► Mice harboring mutations in ribosomal protein Rpl38 display patterning defects ► Global protein synthesis is unchanged in Rpl38 mutant embryos ► RPL38 regulates the translation of Hox mRNAs as part of the ribosome ► Ribosomal proteins show tissue-specific expression patterns in the vertebrate embryo