Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection
Abstract
The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit the ribosome and initiate translation at a non-AUG codon. A subset of dicistrovirus IRESs directs translation in the 0 and +1 frames to produce the viral structural proteins and a +1 overlapping open reading frame called ORFx, respectively. Here we show that specific mutations of two unpaired adenosines located at the core of the three-helical junction of the honey bee dicistrovirusIsraeli acute paralysis virus(IAPV) IRES PKI domain can uncouple 0 and +1 frame translation, suggesting that the structure adopts distinct conformations that contribute to 0 or +1 frame translation. Using a reconstituted translation system, we show that ribosomes assembled on mutant IRESs that direct exclusive 0 or +1 frame translation lack reading frame fidelity. Finally, a nuclear magnetic resonance/small-angle X-ray scattering hybrid approach reveals that the PKI domain of the IAPV IRES adopts an RNA structure that resembles a complete tRNA. Here, the tRNA shape-mimicry enables the viral IRES to gain access to the ribosome tRNA-binding sites and form intermolecular contacts with the ribosome that are necessary for initiating IRES translation in amore »
- Authors:
-
- Univ. of British Columbia, Vancouver, BC (Canada)
- Univ. of Wisconsin, Madison, WI (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- Canadian Institutes of Health Research; Natural Science and Engineering Resources Council Discovery; National Institutes of Health (NIH); USDOE
- OSTI Identifier:
- 1236267
- Grant/Contract Number:
- MOP-81244; RGPIN 341459-12; DMB-8415048; OIA-9977486; S10RR027000; BIR-9214394; GM072447; P41GM103399; S10RR02781; S10RR08438; S10RR023438; S10RR025062; S10RR029220
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 112; Journal Issue: 47; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; translation; virus; RNA; ribosome; internal ribosome entry site
Citation Formats
Au, Hilda H., Cornilescu, Gabriel, Mouzakis, Kathryn D., Ren, Qian, Burke, Jordan E., Lee, Seonghoon, Butcher, Samuel E., and Jan, Eric. Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection. United States: N. p., 2015.
Web. doi:10.1073/pnas.1512088112.
Au, Hilda H., Cornilescu, Gabriel, Mouzakis, Kathryn D., Ren, Qian, Burke, Jordan E., Lee, Seonghoon, Butcher, Samuel E., & Jan, Eric. Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection. United States. https://doi.org/10.1073/pnas.1512088112
Au, Hilda H., Cornilescu, Gabriel, Mouzakis, Kathryn D., Ren, Qian, Burke, Jordan E., Lee, Seonghoon, Butcher, Samuel E., and Jan, Eric. Mon .
"Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection". United States. https://doi.org/10.1073/pnas.1512088112. https://www.osti.gov/servlets/purl/1236267.
@article{osti_1236267,
title = {Global shape mimicry of tRNA within a viral internal ribosome entry site mediates translational reading frame selection},
author = {Au, Hilda H. and Cornilescu, Gabriel and Mouzakis, Kathryn D. and Ren, Qian and Burke, Jordan E. and Lee, Seonghoon and Butcher, Samuel E. and Jan, Eric},
abstractNote = {The dicistrovirus intergenic region internal ribosome entry site (IRES) adopts a triple-pseudoknotted RNA structure and occupies the core ribosomal E, P, and A sites to directly recruit the ribosome and initiate translation at a non-AUG codon. A subset of dicistrovirus IRESs directs translation in the 0 and +1 frames to produce the viral structural proteins and a +1 overlapping open reading frame called ORFx, respectively. Here we show that specific mutations of two unpaired adenosines located at the core of the three-helical junction of the honey bee dicistrovirusIsraeli acute paralysis virus(IAPV) IRES PKI domain can uncouple 0 and +1 frame translation, suggesting that the structure adopts distinct conformations that contribute to 0 or +1 frame translation. Using a reconstituted translation system, we show that ribosomes assembled on mutant IRESs that direct exclusive 0 or +1 frame translation lack reading frame fidelity. Finally, a nuclear magnetic resonance/small-angle X-ray scattering hybrid approach reveals that the PKI domain of the IAPV IRES adopts an RNA structure that resembles a complete tRNA. Here, the tRNA shape-mimicry enables the viral IRES to gain access to the ribosome tRNA-binding sites and form intermolecular contacts with the ribosome that are necessary for initiating IRES translation in a specific reading frame.},
doi = {10.1073/pnas.1512088112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 47,
volume = 112,
place = {United States},
year = {Mon Nov 09 00:00:00 EST 2015},
month = {Mon Nov 09 00:00:00 EST 2015}
}
Web of Science
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