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Cell. 2011 Apr 29;145(3):383-397. doi: 10.1016/j.cell.2011.03.028.

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

Author information

Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.
Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan.
Mammalian Genetics Laboratory, National Institute of Genetics, Mishima Shizuoka-ken 411-8540, Japan.
Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California.
Contributed equally


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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