Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.

Cell 2011 Apr;145(3):383-397

Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.

Historically, 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.

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http://dx.doi.org/10.1016/j.cell.2011.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445650PMC
April 2011
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