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Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo

Like alternative splicing, leaky ribosomal scanning (LRS), which occurs at suboptimal translational initiation codons, increases the physiological flexibility of the genome by allowing alternative translation. Comprehensive analysis of 22 208 human mRNAs indicates that, although the most important p...

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Autores principales: Smith, Elisheva, Meyerrose, Todd E., Kohler, Thomas, Namdar-Attar, Malka, Bab, Natti, Lahat, Olga, Noh, Tommy, Li, Jingjing, Karaman, Mazen W., Hacia, Joseph G., Chen, Ting T., Nolta, Jan A., Müller, Ralph, Bab, Itai, Frenkel, Baruch
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC552952/
https://www.ncbi.nlm.nih.gov/pubmed/15741183
http://dx.doi.org/10.1093/nar/gki248
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author Smith, Elisheva
Meyerrose, Todd E.
Kohler, Thomas
Namdar-Attar, Malka
Bab, Natti
Lahat, Olga
Noh, Tommy
Li, Jingjing
Karaman, Mazen W.
Hacia, Joseph G.
Chen, Ting T.
Nolta, Jan A.
Müller, Ralph
Bab, Itai
Frenkel, Baruch
author_facet Smith, Elisheva
Meyerrose, Todd E.
Kohler, Thomas
Namdar-Attar, Malka
Bab, Natti
Lahat, Olga
Noh, Tommy
Li, Jingjing
Karaman, Mazen W.
Hacia, Joseph G.
Chen, Ting T.
Nolta, Jan A.
Müller, Ralph
Bab, Itai
Frenkel, Baruch
author_sort Smith, Elisheva
collection PubMed
description Like alternative splicing, leaky ribosomal scanning (LRS), which occurs at suboptimal translational initiation codons, increases the physiological flexibility of the genome by allowing alternative translation. Comprehensive analysis of 22 208 human mRNAs indicates that, although the most important positions relative to the first nucleotide of the initiation codon, −3 and +4, are usually such that support initiation (A(−3) = 42%, G(−3) = 36% and G(+4) = 47%), only 37.4% of the genes adhere to the purine (R)(−3)/G(+4) rule at both positions simultaneously, suggesting that LRS may occur in some of the remaining (62.6%) genes. Moreover, 12.5% of the genes lack both R(−3) and G(+4), potentially leading to sLRS. Compared with 11 genes known to undergo LRS, 10 genes with experimental evidence for high fidelity A(+1)T(+2)G(+3) initiation codons adhered much more strongly to the R(−3)/G(+4) rule. Among the intron-less histone genes, only the H3 genes adhere to the R(−3)/G(+4) rule, while the H1, H2A, H2B and H4 genes usually lack either R(−3) or G(+4). To address in vivo the significance of the previously described LRS of H4 mRNAs, which results in alternative translation of the osteogenic growth peptide, transgenic mice were engineered that ubiquitously and constitutively express a mutant H4 mRNA with an A(+1)→T(+1) mutation. These transgenic mice, in particular the females, have a high bone mass phenotype, attributable to increased bone formation. These data suggest that many genes may fulfill cryptic functions by LRS.
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spelling pubmed-5529522005-03-10 Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo Smith, Elisheva Meyerrose, Todd E. Kohler, Thomas Namdar-Attar, Malka Bab, Natti Lahat, Olga Noh, Tommy Li, Jingjing Karaman, Mazen W. Hacia, Joseph G. Chen, Ting T. Nolta, Jan A. Müller, Ralph Bab, Itai Frenkel, Baruch Nucleic Acids Res Article Like alternative splicing, leaky ribosomal scanning (LRS), which occurs at suboptimal translational initiation codons, increases the physiological flexibility of the genome by allowing alternative translation. Comprehensive analysis of 22 208 human mRNAs indicates that, although the most important positions relative to the first nucleotide of the initiation codon, −3 and +4, are usually such that support initiation (A(−3) = 42%, G(−3) = 36% and G(+4) = 47%), only 37.4% of the genes adhere to the purine (R)(−3)/G(+4) rule at both positions simultaneously, suggesting that LRS may occur in some of the remaining (62.6%) genes. Moreover, 12.5% of the genes lack both R(−3) and G(+4), potentially leading to sLRS. Compared with 11 genes known to undergo LRS, 10 genes with experimental evidence for high fidelity A(+1)T(+2)G(+3) initiation codons adhered much more strongly to the R(−3)/G(+4) rule. Among the intron-less histone genes, only the H3 genes adhere to the R(−3)/G(+4) rule, while the H1, H2A, H2B and H4 genes usually lack either R(−3) or G(+4). To address in vivo the significance of the previously described LRS of H4 mRNAs, which results in alternative translation of the osteogenic growth peptide, transgenic mice were engineered that ubiquitously and constitutively express a mutant H4 mRNA with an A(+1)→T(+1) mutation. These transgenic mice, in particular the females, have a high bone mass phenotype, attributable to increased bone formation. These data suggest that many genes may fulfill cryptic functions by LRS. Oxford University Press 2005 2005-03-01 /pmc/articles/PMC552952/ /pubmed/15741183 http://dx.doi.org/10.1093/nar/gki248 Text en © The Author 2005. Published by Oxford University Press. All rights reserved
spellingShingle Article
Smith, Elisheva
Meyerrose, Todd E.
Kohler, Thomas
Namdar-Attar, Malka
Bab, Natti
Lahat, Olga
Noh, Tommy
Li, Jingjing
Karaman, Mazen W.
Hacia, Joseph G.
Chen, Ting T.
Nolta, Jan A.
Müller, Ralph
Bab, Itai
Frenkel, Baruch
Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo
title Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo
title_full Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo
title_fullStr Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo
title_full_unstemmed Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo
title_short Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo
title_sort leaky ribosomal scanning in mammalian genomes: significance of histone h4 alternative translation in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC552952/
https://www.ncbi.nlm.nih.gov/pubmed/15741183
http://dx.doi.org/10.1093/nar/gki248
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