title: Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning.
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.
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.
authors.forename: Nadya
authors.initials: N
authors.lastname: Kondrashov
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.
authors.forename: Aya
authors.initials: A
authors.lastname: Pusic
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Stumpf
authors.affiliation: 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.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hsieh
authors.affiliation: Mammalian Genetics Laboratory, National Institute of Genetics, Mishima Shizuoka-ken 411-8540, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ishijima
authors.affiliation: Mammalian Genetics Laboratory, National Institute of Genetics, Mishima Shizuoka-ken 411-8540, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.affiliation: Department of Biochemistry and Biophysics, Cardiovascular Research Institute, San Francisco, San Francisco, California.
authors.forename: Maria
authors.initials: M
authors.lastname: Barna
mesh_terms: D000818:Animals; D019521:Body Patterning; D001848:Bone Diseases, Developmental / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D038081:Organogenesis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013623:Tail / Q000002:abnormalities
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; C558903:RPL38 protein, mouse; D012269:Ribosomal Proteins