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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

1
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.
2
Department of Pediatric Dentistry, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan.
3
Mammalian Genetics Laboratory, National Institute of Genetics, Mishima Shizuoka-ken 411-8540, Japan.
4
Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California.
#
Contributed equally

Abstract

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.

PMID:
21529712
PMCID:
PMC4445650
DOI:
10.1016/j.cell.2011.03.028
[Indexed for MEDLINE]
Free PMC Article

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