Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.
Nadya Kondrashov, Aya Pusic, Craig R. Stumpf, Kunihiko Shimizu, Andrew C. Hsieh, Junko Ishijima, Toshihiko Shiroishi, and Maria Barna
Cell   Vol.145, 383-397. (2011)  DOI: 10.1016/j.cell.2011.03.028

   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.

Figure. Ribosome-mediated translational control. A, Tail short heterozygote (Ts/+) exhibits short-tail phenotype (left). The Ts/+ phenotype was rescued by transgenesis of the wild-type Rpl38 gene. The transgeneic mouse (right) could not be distinguished from wild-type mouse (middle). B, The Ts/+ mouse (left) exhibits typical anterior homeotic transformation, as represented by 1st lumber with rib (L1 -> Th13). This phenotype was also rescued by transgenesis of the wild-type Rpl38 gene (right). C, Positional cloning revealed that the Ts mutation is caused by a 18kb-deltion in Rpl38 encoding a ribosomal protein. D, A model of ribosome-mediated translational control. Composition of ribosomal proteins constituting ribosome complex differ from tissue to tissue during early mammalian embryogenesis. Each component of ribosome proteins mediates transcript-specific translational control, and imparts a new layer of specificity of the gene expression and mammalian development.