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Control of eukaryotic protein synthesis by upstream open reading frames in the 5'-untranslated region of an mRNA

Abstract

Control of gene expression is achieved at various levels. Translational control becomes crucial in the absence of transcription, such as occurs in early developmental stages. One of the initiating events in translation is that the 40 S subunit of the ribosome binds the mRNA at the 5'-cap structure and scans the 5'-untranslated region (5'-UTR) for AUG initiation codons. AUG codons upstream of the main open reading frame can induce formation of a translation-competent ribosome that may translate and (i) terminate and re-initiate, (ii) terminate and leave the mRNA, resulting in down-regulation of translation of the main open reading frame, or (iii) synthesize an N-terminally extended protein. In the present review we discuss how upstream AUGs can control the expression of the main open reading frame, and a comparison is made with other elements in the 5'-UTR that control mRNA translation, such as hairpins and internal ribosome entry sites. Recent data indicate the flexibility of controlling translation initiation, and how the mode of ribosome entry on the mRNA as well as the elements in the 5'-UTR can accurately regulate the amount of protein synthesized from a specific mRNA.

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Selected References

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  1. Asano K., Clayton J., Shalev A., Hinnebusch A. G. A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo. Genes Dev. 2000 Oct 1;14(19):2534–2546. doi: 10.1101/gad.831800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bag J. Feedback inhibition of poly(A)-binding protein mRNA translation. A possible mechanism of translation arrest by stalled 40 S ribosomal subunits. J Biol Chem. 2001 Oct 4;276(50):47352–47360. doi: 10.1074/jbc.M107676200. [DOI] [PubMed] [Google Scholar]
  3. Belsham G. J., Sonenberg N. Picornavirus RNA translation: roles for cellular proteins. Trends Microbiol. 2000 Jul;8(7):330–335. doi: 10.1016/s0966-842x(00)01788-1. [DOI] [PubMed] [Google Scholar]
  4. Bernstein J., Sella O., Le S. Y., Elroy-Stein O. PDGF2/c-sis mRNA leader contains a differentiation-linked internal ribosomal entry site (D-IRES). J Biol Chem. 1997 Apr 4;272(14):9356–9362. doi: 10.1074/jbc.272.14.9356. [DOI] [PubMed] [Google Scholar]
  5. Bonneau A. M., Sonenberg N. Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis. J Biol Chem. 1987 Aug 15;262(23):11134–11139. [PubMed] [Google Scholar]
  6. Calkhoven C. F., Müller C., Leutz A. Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes Dev. 2000 Aug 1;14(15):1920–1932. [PMC free article] [PubMed] [Google Scholar]
  7. Cao J., Geballe A. P. Inhibition of nascent-peptide release at translation termination. Mol Cell Biol. 1996 Dec;16(12):7109–7114. doi: 10.1128/mcb.16.12.7109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cao J., Geballe A. P. Translational inhibition by a human cytomegalovirus upstream open reading frame despite inefficient utilization of its AUG codon. J Virol. 1995 Feb;69(2):1030–1036. doi: 10.1128/jvi.69.2.1030-1036.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chappell S. A., Edelman G. M., Mauro V. P. A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1536–1541. doi: 10.1073/pnas.97.4.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clemens M. J., Bushell M., Jeffrey I. W., Pain V. M., Morley S. J. Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells. Cell Death Differ. 2000 Jul;7(7):603–615. doi: 10.1038/sj.cdd.4400695. [DOI] [PubMed] [Google Scholar]
  11. Coldwell M. J., Mitchell S. A., Stoneley M., MacFarlane M., Willis A. E. Initiation of Apaf-1 translation by internal ribosome entry. Oncogene. 2000 Feb 17;19(7):899–905. doi: 10.1038/sj.onc.1203407. [DOI] [PubMed] [Google Scholar]
  12. Cornelis S., Bruynooghe Y., Denecker G., Van Huffel S., Tinton S., Beyaert R. Identification and characterization of a novel cell cycle-regulated internal ribosome entry site. Mol Cell. 2000 Apr;5(4):597–605. doi: 10.1016/s1097-2765(00)80239-7. [DOI] [PubMed] [Google Scholar]
  13. Créancier L., Mercier P., Prats A. C., Morello D. c-myc Internal ribosome entry site activity is developmentally controlled and subjected to a strong translational repression in adult transgenic mice. Mol Cell Biol. 2001 Mar;21(5):1833–1840. doi: 10.1128/MCB.21.5.1833-1840.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Créancier L., Morello D., Mercier P., Prats A. C. Fibroblast growth factor 2 internal ribosome entry site (IRES) activity ex vivo and in transgenic mice reveals a stringent tissue-specific regulation. J Cell Biol. 2000 Jul 10;150(1):275–281. doi: 10.1083/jcb.150.1.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Davuluri R. V., Suzuki Y., Sugano S., Zhang M. Q. CART classification of human 5' UTR sequences. Genome Res. 2000 Nov;10(11):1807–1816. doi: 10.1101/gr.gr-1460r. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Degnin C. R., Schleiss M. R., Cao J., Geballe A. P. Translational inhibition mediated by a short upstream open reading frame in the human cytomegalovirus gpUL4 (gp48) transcript. J Virol. 1993 Sep;67(9):5514–5521. doi: 10.1128/jvi.67.9.5514-5521.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fang P., Wang Z., Sachs M. S. Evolutionarily conserved features of the arginine attenuator peptide provide the necessary requirements for its function in translational regulation. J Biol Chem. 2000 Sep 1;275(35):26710–26719. doi: 10.1074/jbc.M003175200. [DOI] [PubMed] [Google Scholar]
  18. Fernandez James, Bode Barry, Koromilas Antonis, Diehl J. Alan, Krukovets Irene, Snider Martin D., Hatzoglou Maria. Translation mediated by the internal ribosome entry site of the cat-1 mRNA is regulated by glucose availability in a PERK kinase-dependent manner. J Biol Chem. 2002 Jan 7;277(14):11780–11787. doi: 10.1074/jbc.M110778200. [DOI] [PubMed] [Google Scholar]
  19. Fernandez James, Yaman Ibrahim, Merrick William C., Koromilas Antonis, Wek Ronald C., Sood Rushira, Hensold Jack, Hatzoglou Maria. Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frame. J Biol Chem. 2001 Oct 29;277(3):2050–2058. doi: 10.1074/jbc.M109199200. [DOI] [PubMed] [Google Scholar]
  20. Fernandez James, Yaman Ibrahim, Sarnow Peter, Snider Martin D., Hatzoglou Maria. Regulation of internal ribosomal entry site-mediated translation by phosphorylation of the translation initiation factor eIF2alpha. J Biol Chem. 2002 Mar 4;277(21):19198–19205. doi: 10.1074/jbc.M201052200. [DOI] [PubMed] [Google Scholar]
  21. Gingras A. C., Raught B., Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001 Apr 1;15(7):807–826. doi: 10.1101/gad.887201. [DOI] [PubMed] [Google Scholar]
  22. Harding H. P., Novoa I., Zhang Y., Zeng H., Wek R., Schapira M., Ron D. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell. 2000 Nov;6(5):1099–1108. doi: 10.1016/s1097-2765(00)00108-8. [DOI] [PubMed] [Google Scholar]
  23. Hill J. R., Morris D. R. Cell-specific translation of S-adenosylmethionine decarboxylase mRNA. Regulation by the 5' transcript leader. J Biol Chem. 1992 Oct 25;267(30):21886–21893. [PubMed] [Google Scholar]
  24. Hohn T., Corsten S., Dominguez D., Fütterer J., Kirk D., Hemmings-Mieszczak M., Pooggin M., Schärer-Hernandez N., Ryabova L. Shunting is a translation strategy used by plant pararetroviruses (Caulimoviridae). Micron. 2001 Jan;32(1):51–57. doi: 10.1016/s0968-4328(00)00020-2. [DOI] [PubMed] [Google Scholar]
  25. Holcik M., Korneluk R. G. Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element: role of La autoantigen in XIAP translation. Mol Cell Biol. 2000 Jul;20(13):4648–4657. doi: 10.1128/mcb.20.13.4648-4657.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Holcik M., Sonenberg N., Korneluk R. G. Internal ribosome initiation of translation and the control of cell death. Trends Genet. 2000 Oct;16(10):469–473. doi: 10.1016/s0168-9525(00)02106-5. [DOI] [PubMed] [Google Scholar]
  27. Johannes G., Sarnow P. Cap-independent polysomal association of natural mRNAs encoding c-myc, BiP, and eIF4G conferred by internal ribosome entry sites. RNA. 1998 Dec;4(12):1500–1513. doi: 10.1017/s1355838298981080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kim J. G., Armstrong R. C., Berndt J. A., Kim N. W., Hudson L. D. A secreted DNA-binding protein that is translated through an internal ribosome entry site (IRES) and distributed in a discrete pattern in the central nervous system. Mol Cell Neurosci. 1998 Oct;12(3):119–140. doi: 10.1006/mcne.1998.0701. [DOI] [PubMed] [Google Scholar]
  29. Kochetov A. V., Ischenko I. V., Vorobiev D. G., Kel A. E., Babenko V. N., Kisselev L. L., Kolchanov N. A. Eukaryotic mRNAs encoding abundant and scarce proteins are statistically dissimilar in many structural features. FEBS Lett. 1998 Dec 4;440(3):351–355. doi: 10.1016/s0014-5793(98)01482-3. [DOI] [PubMed] [Google Scholar]
  30. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kozak M. Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8301–8305. doi: 10.1073/pnas.87.21.8301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kozak M. How do eucaryotic ribosomes select initiation regions in messenger RNA? Cell. 1978 Dec;15(4):1109–1123. doi: 10.1016/0092-8674(78)90039-9. [DOI] [PubMed] [Google Scholar]
  34. Kozak M. Influences of mRNA secondary structure on initiation by eukaryotic ribosomes. Proc Natl Acad Sci U S A. 1986 May;83(9):2850–2854. doi: 10.1073/pnas.83.9.2850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kozak M. Initiation of translation in prokaryotes and eukaryotes. Gene. 1999 Jul 8;234(2):187–208. doi: 10.1016/s0378-1119(99)00210-3. [DOI] [PubMed] [Google Scholar]
  36. Kozak M. New ways of initiating translation in eukaryotes? Mol Cell Biol. 2001 Mar;21(6):1899–1907. doi: 10.1128/MCB.21.6.1899-1907.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  38. Kozak M. Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes. Nucleic Acids Res. 1981 Oct 24;9(20):5233–5252. doi: 10.1093/nar/9.20.5233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Le S. Y., Maizel J. V., Jr A common RNA structural motif involved in the internal initiation of translation of cellular mRNAs. Nucleic Acids Res. 1997 Jan 15;25(2):362–369. doi: 10.1093/nar/25.2.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Maquat L. E., Carmichael G. G. Quality control of mRNA function. Cell. 2001 Jan 26;104(2):173–176. doi: 10.1016/s0092-8674(01)00202-1. [DOI] [PubMed] [Google Scholar]
  41. Meijer H. A., Dictus W. J., Keuning E. D., Thomas A. A. Translational control of the Xenopus laevis connexin-41 5'-untranslated region by three upstream open reading frames. J Biol Chem. 2000 Oct 6;275(40):30787–30793. doi: 10.1074/jbc.M005531200. [DOI] [PubMed] [Google Scholar]
  42. Meiron M., Anunu R., Scheinman E. J., Hashmueli S., Levi B. Z. New isoforms of VEGF are translated from alternative initiation CUG codons located in its 5'UTR. Biochem Biophys Res Commun. 2001 Apr 13;282(4):1053–1060. doi: 10.1006/bbrc.2001.4684. [DOI] [PubMed] [Google Scholar]
  43. Mendez R., Richter J. D. Translational control by CPEB: a means to the end. Nat Rev Mol Cell Biol. 2001 Jul;2(7):521–529. doi: 10.1038/35080081. [DOI] [PubMed] [Google Scholar]
  44. Mikulits W., Schranzhofer M., Beug H., Müllner E. W. Post-transcriptional control via iron-responsive elements: the impact of aberrations in hereditary disease. Mutat Res. 1999 Nov;437(3):219–230. doi: 10.1016/s1383-5742(99)00085-x. [DOI] [PubMed] [Google Scholar]
  45. Miller P. F., Hinnebusch A. G. Sequences that surround the stop codons of upstream open reading frames in GCN4 mRNA determine their distinct functions in translational control. Genes Dev. 1989 Aug;3(8):1217–1225. doi: 10.1101/gad.3.8.1217. [DOI] [PubMed] [Google Scholar]
  46. Mize G. J., Ruan H., Low J. J., Morris D. R. The inhibitory upstream open reading frame from mammalian S-adenosylmethionine decarboxylase mRNA has a strict sequence specificity in critical positions. J Biol Chem. 1998 Dec 4;273(49):32500–32505. doi: 10.1074/jbc.273.49.32500. [DOI] [PubMed] [Google Scholar]
  47. Morris D. R., Geballe A. P. Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol. 2000 Dec;20(23):8635–8642. doi: 10.1128/mcb.20.23.8635-8642.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. O'Neill R. C., Minuk J., Cox M. E., Braun P. E., Gravel M. CNP2 mRNA directs synthesis of both CNP1 and CNP2 polypeptides. J Neurosci Res. 1997 Oct 15;50(2):248–257. doi: 10.1002/(SICI)1097-4547(19971015)50:2<248::AID-JNR13>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  49. Pesole G., Gissi C., Grillo G., Licciulli F., Liuni S., Saccone C. Analysis of oligonucleotide AUG start codon context in eukariotic mRNAs. Gene. 2000 Dec 30;261(1):85–91. doi: 10.1016/s0378-1119(00)00471-6. [DOI] [PubMed] [Google Scholar]
  50. Pesole G., Liuni S., Grillo G., Saccone C. Structural and compositional features of untranslated regions of eukaryotic mRNAs. Gene. 1997 Dec 31;205(1-2):95–102. doi: 10.1016/s0378-1119(97)00407-1. [DOI] [PubMed] [Google Scholar]
  51. Pestova T. V., Kolupaeva V. G., Lomakin I. B., Pilipenko E. V., Shatsky I. N., Agol V. I., Hellen C. U. Molecular mechanisms of translation initiation in eukaryotes. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7029–7036. doi: 10.1073/pnas.111145798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Pilipenko E. V., Pestova T. V., Kolupaeva V. G., Khitrina E. V., Poperechnaya A. N., Agol V. I., Hellen C. U. A cell cycle-dependent protein serves as a template-specific translation initiation factor. Genes Dev. 2000 Aug 15;14(16):2028–2045. [PMC free article] [PubMed] [Google Scholar]
  53. Pooggin M. M., Fütterer J., Skryabin K. G., Hohn T. A short open reading frame terminating in front of a stable hairpin is the conserved feature in pregenomic RNA leaders of plant pararetroviruses. J Gen Virol. 1999 Aug;80(Pt 8):2217–2228. doi: 10.1099/0022-1317-80-8-2217. [DOI] [PubMed] [Google Scholar]
  54. Pooggin M. M., Hohn T., Fütterer J. Role of a short open reading frame in ribosome shunt on the cauliflower mosaic virus RNA leader. J Biol Chem. 2000 Jun 9;275(23):17288–17296. doi: 10.1074/jbc.M001143200. [DOI] [PubMed] [Google Scholar]
  55. Pyronnet S., Pradayrol L., Sonenberg N. A cell cycle-dependent internal ribosome entry site. Mol Cell. 2000 Apr;5(4):607–616. doi: 10.1016/s1097-2765(00)80240-3. [DOI] [PubMed] [Google Scholar]
  56. Raney A., Baron A. C., Mize G. J., Law G. L., Morris D. R. In vitro translation of the upstream open reading frame in the mammalian mRNA encoding S-adenosylmethionine decarboxylase. J Biol Chem. 2000 Aug 11;275(32):24444–24450. doi: 10.1074/jbc.M003364200. [DOI] [PubMed] [Google Scholar]
  57. Raney Alexa, Law G. Lynn, Mize Gregory J., Morris David R. Regulated translation termination at the upstream open reading frame in s-adenosylmethionine decarboxylase mRNA. J Biol Chem. 2001 Dec 12;277(8):5988–5994. doi: 10.1074/jbc.M108375200. [DOI] [PubMed] [Google Scholar]
  58. Reynolds K., Zimmer A. M., Zimmer A. Regulation of RAR beta 2 mRNA expression: evidence for an inhibitory peptide encoded in the 5'-untranslated region. J Cell Biol. 1996 Aug;134(4):827–835. doi: 10.1083/jcb.134.4.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Ruan H., Hill J. R., Fatemie-Nainie S., Morris D. R. 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. J Biol Chem. 1994 Jul 8;269(27):17905–17910. [PubMed] [Google Scholar]
  60. Ruan H., Shantz L. M., Pegg A. E., Morris D. R. The upstream open reading frame of the mRNA encoding S-adenosylmethionine decarboxylase is a polyamine-responsive translational control element. J Biol Chem. 1996 Nov 22;271(47):29576–29582. doi: 10.1074/jbc.271.47.29576. [DOI] [PubMed] [Google Scholar]
  61. Ruiz-Echevarría M. J., Peltz S. W. The RNA binding protein Pub1 modulates the stability of transcripts containing upstream open reading frames. Cell. 2000 Jun 23;101(7):741–751. doi: 10.1016/s0092-8674(00)80886-7. [DOI] [PubMed] [Google Scholar]
  62. Rüegsegger U., Leber J. H., Walter P. Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response. Cell. 2001 Oct 5;107(1):103–114. doi: 10.1016/s0092-8674(01)00505-0. [DOI] [PubMed] [Google Scholar]
  63. Sarrazin S., Starck J., Gonnet C., Doubeikovski A., Melet F., Morle F. Negative and translation termination-dependent positive control of FLI-1 protein synthesis by conserved overlapping 5' upstream open reading frames in Fli-1 mRNA. Mol Cell Biol. 2000 May;20(9):2959–2969. doi: 10.1128/mcb.20.9.2959-2969.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stein I., Itin A., Einat P., Skaliter R., Grossman Z., Keshet E. Translation of vascular endothelial growth factor mRNA by internal ribosome entry: implications for translation under hypoxia. Mol Cell Biol. 1998 Jun;18(6):3112–3119. doi: 10.1128/mcb.18.6.3112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Stoneley M., Chappell S. A., Jopling C. L., Dickens M., MacFarlane M., Willis A. E. c-Myc protein synthesis is initiated from the internal ribosome entry segment during apoptosis. Mol Cell Biol. 2000 Feb;20(4):1162–1169. doi: 10.1128/mcb.20.4.1162-1169.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Suzuki Y., Ishihara D., Sasaki M., Nakagawa H., Hata H., Tsunoda T., Watanabe M., Komatsu T., Ota T., Isogai T. Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries. Genomics. 2000 Mar 15;64(3):286–297. doi: 10.1006/geno.2000.6076. [DOI] [PubMed] [Google Scholar]
  67. Svitkin Y. V., Pause A., Haghighat A., Pyronnet S., Witherell G., Belsham G. J., Sonenberg N. The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in direct proportion to the degree of mRNA 5' secondary structure. RNA. 2001 Mar;7(3):382–394. doi: 10.1017/s135583820100108x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Timchenko N. A., Welm A. L., Lu X., Timchenko L. T. CUG repeat binding protein (CUGBP1) interacts with the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta isoforms. Nucleic Acids Res. 1999 Nov 15;27(22):4517–4525. doi: 10.1093/nar/27.22.4517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Vilela C., Linz B., Rodrigues-Pousada C., McCarthy J. E. The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability. Nucleic Acids Res. 1998 Mar 1;26(5):1150–1159. doi: 10.1093/nar/26.5.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Vilela C., Ramirez C. V., Linz B., Rodrigues-Pousada C., McCarthy J. E. Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA stability. EMBO J. 1999 Jun 1;18(11):3139–3152. doi: 10.1093/emboj/18.11.3139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Wang Z., Fang P., Sachs M. S. The evolutionarily conserved eukaryotic arginine attenuator peptide regulates the movement of ribosomes that have translated it. Mol Cell Biol. 1998 Dec;18(12):7528–7536. doi: 10.1128/mcb.18.12.7528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Wang Z., Gaba A., Sachs M. S. A highly conserved mechanism of regulated ribosome stalling mediated by fungal arginine attenuator peptides that appears independent of the charging status of arginyl-tRNAs. J Biol Chem. 1999 Dec 31;274(53):37565–37574. doi: 10.1074/jbc.274.53.37565. [DOI] [PubMed] [Google Scholar]
  73. Wells S. E., Hillner P. E., Vale R. D., Sachs A. B. Circularization of mRNA by eukaryotic translation initiation factors. Mol Cell. 1998 Jul;2(1):135–140. doi: 10.1016/s1097-2765(00)80122-7. [DOI] [PubMed] [Google Scholar]
  74. Wilson J. E., Pestova T. V., Hellen C. U., Sarnow P. Initiation of protein synthesis from the A site of the ribosome. Cell. 2000 Aug 18;102(4):511–520. doi: 10.1016/s0092-8674(00)00055-6. [DOI] [PubMed] [Google Scholar]
  75. Ye X., Fong P., Iizuka N., Choate D., Cavener D. R. Ultrabithorax and Antennapedia 5' untranslated regions promote developmentally regulated internal translation initiation. Mol Cell Biol. 1997 Mar;17(3):1714–1721. doi: 10.1128/mcb.17.3.1714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Yueh A., Schneider R. J. Translation by ribosome shunting on adenovirus and hsp70 mRNAs facilitated by complementarity to 18S rRNA. Genes Dev. 2000 Feb 15;14(4):414–421. [PMC free article] [PubMed] [Google Scholar]
  77. Zimmer A., Zimmer A. M., Reynolds K. Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5'-noncoding region. J Cell Biol. 1994 Nov;127(4):1111–1119. doi: 10.1083/jcb.127.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. van der Velden A. W., Destrée OHJ, Voorma H. O., Thomas A. A. Controlled translation initiation on insulin-like growth factor 2-leader 1 during Xenopus laevis embryogenesis. Int J Dev Biol. 2000 Dec;44(8):843–850. [PubMed] [Google Scholar]
  79. van der Velden A. W., Los A., Voorma H. O., Thomas A. A. Sequence and translation initiation properties of the xenopus TGFbeta5, PDGF-A, and PDGF-alpha receptor 5' untranslated regions. Int J Dev Biol. 2000 Dec;44(8):851–859. [PubMed] [Google Scholar]