Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism

Research output: Contribution to journalJournal articleResearchpeer-review

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Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism. / Belsham, Graham J; Nielsen, Inge; Normann, Preben; Royall, Elizabeth; Roberts, Lisa O.

In: R N A, Vol. 14, No. 8, 08.2008, p. 1671-80.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Belsham, GJ, Nielsen, I, Normann, P, Royall, E & Roberts, LO 2008, 'Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism', R N A, vol. 14, no. 8, pp. 1671-80. https://doi.org/10.1261/rna.1039708

APA

Belsham, G. J., Nielsen, I., Normann, P., Royall, E., & Roberts, L. O. (2008). Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism. R N A, 14(8), 1671-80. https://doi.org/10.1261/rna.1039708

Vancouver

Belsham GJ, Nielsen I, Normann P, Royall E, Roberts LO. Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism. R N A. 2008 Aug;14(8):1671-80. https://doi.org/10.1261/rna.1039708

Author

Belsham, Graham J ; Nielsen, Inge ; Normann, Preben ; Royall, Elizabeth ; Roberts, Lisa O. / Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism. In: R N A. 2008 ; Vol. 14, No. 8. pp. 1671-80.

Bibtex

@article{903c632398764ae6ad001bf21c4b88df,
title = "Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism",
abstract = "The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved either by a 5' cap-dependent mechanism or through internal initiation directed by an internal ribosome entry site (IRES). Picornavirus IRES elements, located in the 5' untranslated region (5'UTR), contain extensive secondary structure and multiple upstream AUG codons. These features can be expected to inhibit cap-dependent initiation of translation. However, we have now shown that certain mutant hepatitis C virus-like picornavirus IRES elements (from porcine teschovirus-1 and avian encephalomyelitis virus), which are unable to direct internal initiation, are not significant barriers to efficient translation of capped monocistronic mRNAs that contain these defective elements within their 5'UTRs. Moreover, the translation of these mRNAs is highly sensitive to the expression of an enterovirus 2A protease (which induces cleavage of eIF4G) and is also inhibited by hippuristanol, a specific inhibitor of eIF4A function, in contrast to their parental wild-type IRES elements. These results provide a possible basis for the evolution of viral IRES elements within the context of functional mRNAs that are translated by a cap-dependent mechanism.",
keywords = "5' Untranslated Regions/chemistry, Eukaryotic Initiation Factor-4G/antagonists & inhibitors, Humans, Peptide Chain Initiation, Translational, Picornaviridae/chemistry, Protein Biosynthesis, RNA Caps/metabolism, RNA, Messenger/chemistry, Regulatory Sequences, Ribonucleic Acid, Ribosomes/metabolism, Sterols/pharmacology",
author = "Belsham, {Graham J} and Inge Nielsen and Preben Normann and Elizabeth Royall and Roberts, {Lisa O}",
year = "2008",
month = aug,
doi = "10.1261/rna.1039708",
language = "English",
volume = "14",
pages = "1671--80",
journal = "R N A",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "8",

}

RIS

TY - JOUR

T1 - Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5' untranslated regions are efficiently translated in cells by a cap-dependent mechanism

AU - Belsham, Graham J

AU - Nielsen, Inge

AU - Normann, Preben

AU - Royall, Elizabeth

AU - Roberts, Lisa O

PY - 2008/8

Y1 - 2008/8

N2 - The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved either by a 5' cap-dependent mechanism or through internal initiation directed by an internal ribosome entry site (IRES). Picornavirus IRES elements, located in the 5' untranslated region (5'UTR), contain extensive secondary structure and multiple upstream AUG codons. These features can be expected to inhibit cap-dependent initiation of translation. However, we have now shown that certain mutant hepatitis C virus-like picornavirus IRES elements (from porcine teschovirus-1 and avian encephalomyelitis virus), which are unable to direct internal initiation, are not significant barriers to efficient translation of capped monocistronic mRNAs that contain these defective elements within their 5'UTRs. Moreover, the translation of these mRNAs is highly sensitive to the expression of an enterovirus 2A protease (which induces cleavage of eIF4G) and is also inhibited by hippuristanol, a specific inhibitor of eIF4A function, in contrast to their parental wild-type IRES elements. These results provide a possible basis for the evolution of viral IRES elements within the context of functional mRNAs that are translated by a cap-dependent mechanism.

AB - The initiation of protein synthesis on mRNAs within eukaryotic cells is achieved either by a 5' cap-dependent mechanism or through internal initiation directed by an internal ribosome entry site (IRES). Picornavirus IRES elements, located in the 5' untranslated region (5'UTR), contain extensive secondary structure and multiple upstream AUG codons. These features can be expected to inhibit cap-dependent initiation of translation. However, we have now shown that certain mutant hepatitis C virus-like picornavirus IRES elements (from porcine teschovirus-1 and avian encephalomyelitis virus), which are unable to direct internal initiation, are not significant barriers to efficient translation of capped monocistronic mRNAs that contain these defective elements within their 5'UTRs. Moreover, the translation of these mRNAs is highly sensitive to the expression of an enterovirus 2A protease (which induces cleavage of eIF4G) and is also inhibited by hippuristanol, a specific inhibitor of eIF4A function, in contrast to their parental wild-type IRES elements. These results provide a possible basis for the evolution of viral IRES elements within the context of functional mRNAs that are translated by a cap-dependent mechanism.

KW - 5' Untranslated Regions/chemistry

KW - Eukaryotic Initiation Factor-4G/antagonists & inhibitors

KW - Humans

KW - Peptide Chain Initiation, Translational

KW - Picornaviridae/chemistry

KW - Protein Biosynthesis

KW - RNA Caps/metabolism

KW - RNA, Messenger/chemistry

KW - Regulatory Sequences, Ribonucleic Acid

KW - Ribosomes/metabolism

KW - Sterols/pharmacology

U2 - 10.1261/rna.1039708

DO - 10.1261/rna.1039708

M3 - Journal article

C2 - 18567818

VL - 14

SP - 1671

EP - 1680

JO - R N A

JF - R N A

SN - 1355-8382

IS - 8

ER -

ID: 257918409