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. 2000 Mar 15;346(Pt 3):849–855.

Internal-ribosome-entry-site functional activity of the 3'-untranslated region of the mRNA for the beta subunit of mitochondrial H+-ATP synthase.

J M Izquierdo 1, J M Cuezva 1
PMCID: PMC1220922  PMID: 10698716

Abstract

Translation in vitro of the mammalian nucleus-encoded mRNA for the beta subunit of mitochondrial H(+)-ATP synthase (beta-mRNA) of oxidative phosphorylation is promoted by a 150 nt translational enhancer sequence in the 3'-untranslated region (3' UTR). Titration of the eukaryotic initiation factor eIF4E with cap analogue revealed that translation of capped beta-mRNA was pseudo-cap independent. The 3' UTR of beta-mRNA stimulates the translation of heterologous uncapped mRNA species, both when the 3' UTR is placed at the 3' end and at the 5' end of the transcripts. The 3' UTRs of the alpha subunit of mitochondrial H(+)-ATP synthase (alpha-F1-ATPase) and subunit IV of cytochrome c oxidase (COX IV) mRNA species, other nucleus-encoded transcripts of oxidative phosphorylation, do not have the same activity in translation as the 3' UTR of beta-mRNA. On dicistronic RNA species, the 3' UTR of beta-mRNA, and to a smaller extent that of COX IV mRNA, is able to promote the translation of the second cistron to a level comparable to the activity of internal ribosome entry sites (IRESs) described in picornavirus mRNA species. These results indicate that the 3' UTRs of certain mRNA species of oxidative phosphorylation have IRES-like functional activity. Riboprobes of the active 3' UTRs on dicistronic assays formed specific RNA-protein complexes when cross-linked by UV to proteins of the lysate, suggesting that cytoplasmic translation of the mRNA species bearing an active 3' UTR is assisted by specific RNA-protein interactions.

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Selected References

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  1. Asselbergs F. A., Peters W., Venrooij W. J., Bloemendal H. Diminished sensitivity of re-initiation of translation to inhibition by cap analogues in reticulocyte lysates. Eur J Biochem. 1978 Aug 1;88(2):483–488. doi: 10.1111/j.1432-1033.1978.tb12473.x. [DOI] [PubMed] [Google Scholar]
  2. Borman A. M., Bailly J. L., Girard M., Kean K. M. Picornavirus internal ribosome entry segments: comparison of translation efficiency and the requirements for optimal internal initiation of translation in vitro. Nucleic Acids Res. 1995 Sep 25;23(18):3656–3663. doi: 10.1093/nar/23.18.3656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chung A. B., Stepien G., Haraguchi Y., Li K., Wallace D. C. Transcriptional control of nuclear genes for the mitochondrial muscle ADP/ATP translocator and the ATP synthase beta subunit. Multiple factors interact with the OXBOX/REBOX promoter sequences. J Biol Chem. 1992 Oct 15;267(29):21154–21161. [PubMed] [Google Scholar]
  4. Craig A. W., Haghighat A., Yu A. T., Sonenberg N. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature. 1998 Apr 2;392(6675):520–523. doi: 10.1038/33198. [DOI] [PubMed] [Google Scholar]
  5. Cuezva J. M., Ostronoff L. K., Ricart J., López de Heredia M., Di Liegro C. M., Izquierdo J. M. Mitochondrial biogenesis in the liver during development and oncogenesis. J Bioenerg Biomembr. 1997 Aug;29(4):365–377. doi: 10.1023/a:1022450831360. [DOI] [PubMed] [Google Scholar]
  6. Danthinne X., Seurinck J., Meulewaeter F., Van Montagu M., Cornelissen M. The 3' untranslated region of satellite tobacco necrosis virus RNA stimulates translation in vitro. Mol Cell Biol. 1993 Jun;13(6):3340–3349. doi: 10.1128/mcb.13.6.3340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Egea G., Izquierdo J. M., Ricart J., San Martín C., Cuezva J. M. mRNA encoding the beta-subunit of the mitochondrial F1-ATPase complex is a localized mRNA in rat hepatocytes. Biochem J. 1997 Mar 1;322(Pt 2):557–565. doi: 10.1042/bj3220557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gallie D. R. A tale of two termini: a functional interaction between the termini of an mRNA is a prerequisite for efficient translation initiation. Gene. 1998 Aug 17;216(1):1–11. doi: 10.1016/s0378-1119(98)00318-7. [DOI] [PubMed] [Google Scholar]
  9. Gallie D. R. The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. Genes Dev. 1991 Nov;5(11):2108–2116. doi: 10.1101/gad.5.11.2108. [DOI] [PubMed] [Google Scholar]
  10. Goto Y., Amuro N., Okazaki T. Nucleotide sequence of cDNA for rat brain and liver cytochrome c oxidase subunit IV. Nucleic Acids Res. 1989 Apr 11;17(7):2851–2851. doi: 10.1093/nar/17.7.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haghighat A., Mader S., Pause A., Sonenberg N. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 1995 Nov 15;14(22):5701–5709. doi: 10.1002/j.1460-2075.1995.tb00257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haghighat A., Svitkin Y., Novoa I., Kuechler E., Skern T., Sonenberg N. The eIF4G-eIF4E complex is the target for direct cleavage by the rhinovirus 2A proteinase. J Virol. 1996 Dec;70(12):8444–8450. doi: 10.1128/jvi.70.12.8444-8450.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hann L. E., Webb A. C., Cai J. M., Gehrke L. Identification of a competitive translation determinant in the 3' untranslated region of alfalfa mosaic virus coat protein mRNA. Mol Cell Biol. 1997 Apr;17(4):2005–2013. doi: 10.1128/mcb.17.4.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hellen C. U., Wimmer E. Translation of encephalomyocarditis virus RNA by internal ribosomal entry. Curr Top Microbiol Immunol. 1995;203:31–63. doi: 10.1007/978-3-642-79663-0_2. [DOI] [PubMed] [Google Scholar]
  15. Hentze M. W. eIF4G: a multipurpose ribosome adapter? Science. 1997 Jan 24;275(5299):500–501. doi: 10.1126/science.275.5299.500. [DOI] [PubMed] [Google Scholar]
  16. Iizuka N., Chen C., Yang Q., Johannes G., Sarnow P. Cap-independent translation and internal initiation of translation in eukaryotic cellular mRNA molecules. Curr Top Microbiol Immunol. 1995;203:155–177. doi: 10.1007/978-3-642-79663-0_8. [DOI] [PubMed] [Google Scholar]
  17. Izquierdo J. M., Cuezva J. M. Control of the translational efficiency of beta-F1-ATPase mRNA depends on the regulation of a protein that binds the 3' untranslated region of the mRNA. Mol Cell Biol. 1997 Sep;17(9):5255–5268. doi: 10.1128/mcb.17.9.5255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Izquierdo J. M., Cuezva J. M. Evidence of post-transcriptional regulation in mammalian mitochondrial biogenesis. Biochem Biophys Res Commun. 1993 Oct 15;196(1):55–60. doi: 10.1006/bbrc.1993.2215. [DOI] [PubMed] [Google Scholar]
  19. Izquierdo J. M., Cuezva J. M. Thyroid hormones promote transcriptional activation of the nuclear gene coding for mitochondrial beta-F1-ATPase in rat liver. FEBS Lett. 1993 May 24;323(1-2):109–112. doi: 10.1016/0014-5793(93)81459-d. [DOI] [PubMed] [Google Scholar]
  20. Izquierdo J. M., Ricart J., Ostronoff L. K., Egea G., Cuezva J. M. Changing patterns of transcriptional and post-transcriptional control of beta-F1-ATPase gene expression during mitochondrial biogenesis in liver. J Biol Chem. 1995 Apr 28;270(17):10342–10350. doi: 10.1074/jbc.270.17.10342. [DOI] [PubMed] [Google Scholar]
  21. Jackson R. J., Hunt S. L., Reynolds J. E., Kaminski A. Cap-dependent and cap-independent translation: operational distinctions and mechanistic interpretations. Curr Top Microbiol Immunol. 1995;203:1–29. doi: 10.1007/978-3-642-79663-0_1. [DOI] [PubMed] [Google Scholar]
  22. Jackson R. J., Kaminski A. Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond. RNA. 1995 Dec;1(10):985–1000. [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Joshi-Barve S., De Benedetti A., Rhoads R. E. Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF-4 gamma. J Biol Chem. 1992 Oct 15;267(29):21038–21043. [PubMed] [Google Scholar]
  25. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lee J. H., Garboczi D. N., Thomas P. J., Pedersen P. L. Mitochondrial ATP synthase. cDNA cloning, amino acid sequence, overexpression, and properties of the rat liver alpha subunit. J Biol Chem. 1990 Mar 15;265(8):4664–4669. [PubMed] [Google Scholar]
  27. Luis A. M., Izquierdo J. M., Ostronoff L. K., Salinas M., Santarén J. F., Cuezva J. M. Translational regulation of mitochondrial differentiation in neonatal rat liver. Specific increase in the translational efficiency of the nuclear-encoded mitochondrial beta-F1-ATPase mRNA. J Biol Chem. 1993 Jan 25;268(3):1868–1875. [PubMed] [Google Scholar]
  28. Martínez-Salas E., Sáiz J. C., Dávila M., Belsham G. J., Domingo E. A single nucleotide substitution in the internal ribosome entry site of foot-and-mouth disease virus leads to enhanced cap-independent translation in vivo. J Virol. 1993 Jul;67(7):3748–3755. doi: 10.1128/jvi.67.7.3748-3755.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Matsuyama S., Xu Q., Velours J., Reed J. C. The Mitochondrial F0F1-ATPase proton pump is required for function of the proapoptotic protein Bax in yeast and mammalian cells. Mol Cell. 1998 Feb;1(3):327–336. doi: 10.1016/s1097-2765(00)80033-7. [DOI] [PubMed] [Google Scholar]
  30. Meulewaeter F., Van Montagu M., Cornelissen M. Features of the autonomous function of the translational enhancer domain of satellite tobacco necrosis virus. RNA. 1998 Nov;4(11):1347–1356. doi: 10.1017/s135583829898092x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pelletier J., Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988 Jul 28;334(6180):320–325. doi: 10.1038/334320a0. [DOI] [PubMed] [Google Scholar]
  32. Preiss T., Hentze M. W. Dual function of the messenger RNA cap structure in poly(A)-tail-promoted translation in yeast. Nature. 1998 Apr 2;392(6675):516–520. doi: 10.1038/33192. [DOI] [PubMed] [Google Scholar]
  33. Preiss T., Muckenthaler M., Hentze M. W. Poly(A)-tail-promoted translation in yeast: implications for translational control. RNA. 1998 Nov;4(11):1321–1331. doi: 10.1017/s1355838298980669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ricart J., Egea G., Izquierdo J. M., San Martín C., Cuezva J. M. Subcellular structure containing mRNA for beta subunit of mitochondrial H+-ATP synthase in rat hepatocytes is translationally active. Biochem J. 1997 Jun 1;324(Pt 2):635–643. doi: 10.1042/bj3240635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rojo G., Chamorro M., Salas M. L., Viñuela E., Cuezva J. M., Salas J. Migration of mitochondria to viral assembly sites in African swine fever virus-infected cells. J Virol. 1998 Sep;72(9):7583–7588. doi: 10.1128/jvi.72.9.7583-7588.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sachs A. B., Sarnow P., Hentze M. W. Starting at the beginning, middle, and end: translation initiation in eukaryotes. Cell. 1997 Jun 13;89(6):831–838. doi: 10.1016/s0092-8674(00)80268-8. [DOI] [PubMed] [Google Scholar]
  37. Tarun S. Z., Jr, Sachs A. B. A common function for mRNA 5' and 3' ends in translation initiation in yeast. Genes Dev. 1995 Dec 1;9(23):2997–3007. doi: 10.1101/gad.9.23.2997. [DOI] [PubMed] [Google Scholar]
  38. Tarun S. Z., Jr, Sachs A. B. Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J. 1996 Dec 16;15(24):7168–7177. [PMC free article] [PubMed] [Google Scholar]
  39. Tvrdík P., Kuzela S., Houstek J. Low translational efficiency of the F1-ATPase beta-subunit mRNA largely accounts for the decreased ATPase content in brown adipose tissue mitochondria. FEBS Lett. 1992 Nov 16;313(1):23–26. doi: 10.1016/0014-5793(92)81175-l. [DOI] [PubMed] [Google Scholar]
  40. Villena J. A., Martin I., Viñas O., Cormand B., Iglesias R., Mampel T., Giralt M., Villarroya F. ETS transcription factors regulate the expression of the gene for the human mitochondrial ATP synthase beta-subunit. J Biol Chem. 1994 Dec 23;269(51):32649–32654. [PubMed] [Google Scholar]
  41. Wang S., Browning K. S., Miller W. A. A viral sequence in the 3'-untranslated region mimics a 5' cap in facilitating translation of uncapped mRNA. EMBO J. 1997 Jul 1;16(13):4107–4116. doi: 10.1093/emboj/16.13.4107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wang S., Guo L., Allen E., Miller W. A. A potential mechanism for selective control of cap-independent translation by a viral RNA sequence in cis and in trans. RNA. 1999 Jun;5(6):728–738. doi: 10.1017/s1355838299981979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wang S., Miller W. A. A sequence located 4.5 to 5 kilobases from the 5' end of the barley yellow dwarf virus (PAV) genome strongly stimulates translation of uncapped mRNA. J Biol Chem. 1995 Jun 2;270(22):13446–13452. doi: 10.1074/jbc.270.22.13446. [DOI] [PubMed] [Google Scholar]
  44. 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]

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