Control of gene expression at the level of translation initiation.

Protein synthesis is controlled at the level of translation initiation. Cells rapidly respond to environmental changes by disassembly of polysomes and recruitment of specific mRNAs from inactive ribonucleoprotein particles into polysomes active in translation. Recent insights have elucidated specific protein and RNA sequence interactions that are required to mobilize translation of selective mRNAs. The specificity of translational control provides a unique target to inhibit synthesis of specific polypeptides to control infectious disease as well as to control aberrant cell growth. In addition, greater understanding of the factors that limit protein synthesis is enabling the design of novel strategies to optimize protein expression and engineer host cells for enhanced growth and protein synthesis capacity.

[1]  A. De Benedetti,et al.  Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma. , 1992, Journal of Biological Chemistry.

[2]  W. Merrick.  Mechanism and regulation of eukaryotic protein synthesis. , 1992, Microbiological reviews.

[3]  N. Sonenberg,et al.  The HRIGRXXR region of the DEAD box RNA helicase eukaryotic translation initiation factor 4A is required for RNA binding and ATP hydrolysis , 1993, Molecular and cellular biology.

[4]  E. Paoletti,et al.  TAR RNA-binding protein is an inhibitor of the interferon-induced protein kinase PKR. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[5]  D. Chakrabarti,et al.  Cloning and characterization of complementary DNA encoding the eukaryotic initiation factor 2-associated 67-kDa protein (p67). , 1993, The Journal of biological chemistry.

[6]  A. Jacobson,et al.  mRNA poly(A) tail, a 3' enhancer of translational initiation , 1990, Molecular and cellular biology.

[7]  E. Wimmer,et al.  Genetics of poliovirus. , 1993, Annual review of genetics.

[8]  G. Thomas,et al.  Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M J Clemens,et al.  Comparative analysis of the regulation of the interferon-inducible protein kinase PKR by Epstein-Barr virus RNAs EBER-1 and EBER-2 and adenovirus VAI RNA. , 1993, Nucleic acids research.

[10]  A. Prats,et al.  cis-acting elements involved in the alternative translation initiation process of human basic fibroblast growth factor mRNA , 1992, Molecular and cellular biology.

[11]  A. Shatkin,et al.  Translational stimulation by reovirus polypeptide sigma 3: substitution for VAI RNA and inhibition of phosphorylation of the alpha subunit of eukaryotic initiation factor 2 , 1992, Journal of virology.

[12]  C. Samuel,et al.  Mechanism of interferon action. Translational control and the RNA-dependent protein kinase (PKR): antagonists of PKR enhance the translational activity of mRNAs that include a 161 nucleotide region from reovirus S1 mRNA. , 1994, Journal of biological regulators and homeostatic agents.

[13]  M. Kozak.  A consideration of alternative models for the initiation of translation in eukaryotes. , 1992, Critical reviews in biochemistry and molecular biology.

[14]  M. Katze,et al.  Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Kaufman,et al.  Internal translation initiation in the design of improved expression vectors. , 1992, Current opinion in biotechnology.

[16]  N. Sonenberg,et al.  Internal initiation of picornavirus RNA translation , 1993 .

[17]  R. Petryshyn,et al.  Mechanism of action of a cellular inhibitor of the dsRNA-dependent protein kinase from 3T3-F442A cells. , 1992, The Journal of biological chemistry.

[18]  M. Mathews,et al.  Two RNA-binding motifs in the double-stranded RNA-activated protein kinase, DAI. , 1992, Genes & development.

[19]  R. Klausner,et al.  Regulating the fate of mRNA: The control of cellular iron metabolism , 1993, Cell.

[20]  M. Kozak.  Structural features in eukaryotic mRNAs that modulate the initiation of translation. , 1991, The Journal of biological chemistry.

[21]  J. Hershey,et al.  Translational control in mammalian cells. , 1991, Annual review of biochemistry.

[22]  N. Sonenberg,et al.  Dominant negative mutants of mammalian translation initiation factor eIF‐4A define a critical role for eIF‐4F in cap‐dependent and cap‐independent initiation of translation. , 1994, The EMBO journal.

[23]  E. Wimmer,et al.  A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  C. Samuel,et al.  The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. , 1993, The Journal of biological chemistry.

[25]  R. Kaufman,et al.  Characterization of wild-type and Ser53 mutant eukaryotic initiation factor 4E overexpression in mammalian cells. , 1993, The Journal of biological chemistry.

[26]  P. Sarnow,et al.  Internal initiation of translation mediated by the 5′ leader of a cellular mRNA , 1991, Nature.

[27]  J. Hershey,et al.  Expression of a phosphorylation-resistant eukaryotic initiation factor 2 alpha-subunit mitigates heat shock inhibition of protein synthesis. , 1993, The Journal of biological chemistry.

[28]  N. Sonenberg,et al.  Ras mediates translation initiation factor 4E-induced malignant transformation. , 1992, Genes & development.

[29]  A. De Benedetti,et al.  Decreasing the level of translation initiation factor 4E with antisense rna causes reversal of ras‐mediated transformation and tumorigenesis of cloned rat embryo fibroblasts , 1993, International journal of cancer.

[30]  M. Mathews,et al.  Interactions between double-stranded RNA regulators and the protein kinase DAI , 1992, Molecular and cellular biology.

[31]  Z. Xu,et al.  Denatured proteins inhibit translation in hemin-supplemented rabbit reticulocyte lysate by inducing the activation of the heme-regulated eIF-2 alpha kinase. , 1993, Biochemistry.

[32]  R. Rhoads,et al.  Mapping the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus. , 1993, The Journal of biological chemistry.

[33]  A. Prats,et al.  Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes , 1995, Molecular and cellular biology.

[34]  mRNA poly(A) tail, a 3' enhancer of translational initiation. , 1990 .

[35]  J. Nichols,et al.  Dicistronic targeting constructs: reporters and modifiers of mammalian gene expression. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G. Feng,et al.  Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  H. W. Chang,et al.  The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms , 1993, Journal of virology.

[38]  S. Daniels-McQueen,et al.  Inducible expression bovine papillomavirus shuttle vectors containing ferritin translational regulatory elements. , 1992, Gene.

[39]  M. Katze,et al.  Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. , 1992, Science.

[40]  Robert L. Tanguay,et al.  Poly(A) binds to initiation factors and increases cap-dependent translation in vitro. , 1994, The Journal of biological chemistry.

[41]  V. Agol,et al.  Internal translation initiation on poliovirus RNA: further characterization of La function in poliovirus translation in vitro , 1994, Journal of virology.

[42]  R. Rhoads.  Regulation of eukaryotic protein synthesis by initiation factors. , 1993, The Journal of biological chemistry.

[43]  R. Silverman,et al.  Blockage of NF-kappa B signaling by selective ablation of an mRNA target by 2-5A antisense chimeras. , 1994, Science.

[44]  R. Kaufman,et al.  Expression of mutant eukaryotic initiation factor 2 alpha subunit (eIF-2 alpha) reduces inhibition of guanine nucleotide exchange activity of eIF-2B mediated by eIF-2 alpha phosphorylation , 1994, Molecular and cellular biology.

[45]  H. Prats,et al.  Involvement of basic fibroblast growth factor NH2 terminus in nuclear accumulation. , 1994, Growth factors.

[46]  M. Katze,et al.  The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins , 1994, Molecular and cellular biology.

[47]  Aseem Kumar,et al.  Double-stranded RNA-dependent protein kinase activates transcription factor NF-kappa B by phosphorylating I kappa B. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[48]  G. Scheper,et al.  Eukaryotic initiation factors-4E and -4F stimulate 5' cap-dependent as well as internal initiation of protein synthesis. , 1992, The Journal of biological chemistry.

[49]  N. Sonenberg,et al.  The mRNA 5' cap-binding protein, eIF-4E, cooperates with v-myc or E1A in the transformation of primary rodent fibroblasts , 1992, Molecular and cellular biology.

[50]  R. Jackson,et al.  Do the poly(A) tail and 3′ untranslated region control mRNA translation? , 1990, Cell.

[51]  J. Hill,et al.  Cell-specific translational regulation of S-adenosylmethionine decarboxylase mRNA. Influence of the structure of the 5' transcript leader on regulation by the upstream open reading frame. , 1993, The Journal of biological chemistry.

[52]  D. Faller,et al.  Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic initiation factor 2 alpha-kinase activation. , 1992, The Journal of biological chemistry.

[53]  D. Melton,et al.  Induction of mesoderm in Xenopus laevis embryos by translation initiation factor 4E. , 1994, Science.

[54]  M. Scott,et al.  Homeotic gene Antennapedia mRNA contains 5'-noncoding sequences that confer translational initiation by internal ribosome binding. , 1992, Genes & development.

[55]  P. Sarnow,et al.  Internal initiation of translation. , 1993, Current opinion in cell biology.

[56]  M. Katze,et al.  The 58-kilodalton inhibitor of the interferon-induced double-stranded RNA-activated protein kinase is a tetratricopeptide repeat protein with oncogenic properties. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[57]  A. Hinnebusch,et al.  Mutations in the GCD7 subunit of yeast guanine nucleotide exchange factor eIF-2B overcome the inhibitory effects of phosphorylated eIF-2 on translation initiation , 1994, Molecular and cellular biology.