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Non-canonical virus translation

3' Cap-independent translation enhancers (3'CITEs)

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The best studied translation elements in plant viruses are the 3′ proximal CITEs. Viruses can contain one or multiple 3′CITEs, with the three 3′CITEs of pea enation mosaic umbravirus (PEMV2) used differentially for translation of the gRNA and the sgRNA.  3′CITEs are grouped according to their secondary structures and abilities to bind to particular translation components, usually eukaryotic translation initiation factor 4F (eIF4F) through either its eIF4E or eIF4G subunits, or directly to ribosomal subunits. Not all 3′CITEs of a certain type share conserved features, as demonstrated by panicum mosaic virus (family Tombusviridae) translation enhancers (PTEs), some of which contain an additional hairpin and kissing-loop interaction, and barley yellow dwarf virus translation enhancers (BTEs), which contain at least three different sub-types that share signature features but also contain their own distinctive conserved sequences. Virus members of the carmovirus genus share highly conserved structures at their 3′ termini and yet have different 3′CITEs just upstream including the T-shaped ribosome binding structure (TSS) found in turnip crinkle virus and also in many umbraviruses, suggesting that recombination has played an important role in the addition of 3′CITEs to plant virus genomes. While it was generally accepted that long-distance RNA:RNA interactions that join most 3'CITEs with 5' proximal sequences thus circularizing viral templates would enhance the translation initiation rate leading to an increase in the number of ribosomes occupying the template, disruption of the long-distance interaction in PEMV2 had no effect on ribosome occupancy but significantly reduced the overall number of translated templates. The presence of key translation elements near the 3′ end of the viral genome ensures that both viral and subviral RNAs have access to the elements, and the close proximity or overlapping of translation elements with structures required for RdRp-mediated transcription from the 3′ end of the genome allows for conformational rearrangements that remove translation factors that could interfere with replication

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Publications:

 

  • Bera, S., Ilyas, M., Mikklesen, A.A., and Simon, A.E.  2023.  Conserved structure associated with different 3’CITEs is important for translation of umbraviruses.  Viruses 15: 638.  doi: 10.3390/v15030638

  • Simon, A.E., Makinen, K., and Verchot, J.M. 2023. Chapter 18: Plant Viruses. In: Field’s Virology, 7th Edition. Eds David M. Knipe, Peter M. Howley. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, USA.

  • Johnson, P.Z., Reuning, H.M., Bera, S., Gao, F., Du, Z., and Simon. A.E. (2022) Novel 3´ proximal replication elements in umbravirus genomes. Viruses 14, 2615 doi.org/10.3390/v14122615 [Journal cover selection]​

  • Liu, J., and Simon, A.E.  2022.  Identification of Novel 5ʹ and 3ʹ Translation Enhancers in Umbravirus-like Coat-Protein-Dependent RNA Replicons.  J Virol 96, e0173621   doi: 10.1128/jvi.01736-21.

  • Johnson, P., Kasprzak, W.K., Shapiro, B.A., and Simon, A.E. 2022.  Structural characterization of a new class of PTE 3’ cap independent translation enhancers.  Nucleic Acids Res 50, 1601-1619.

  • ​Ilyas, M, Du, Z. and Simon, A.E. 2021.  Opium poppy mosaic virus has an Xrn-resistant, translated subgenomic RNA and a BTE 3’ CITE.  J Virol  95 (9): e02109-20 doi: 10.1128/JVI.02109-20 [SPOTLIGHT selection]

  • ​Gao, F., Alekhina, O.M., Vassilenko, K.S., and Simon, A.E.  2018. Unusual dicistronic expression from closely-spaced initiation codons of overlapping open reading frames in Pea enation mosaic virus 2.  Nucleic Acids Res 46, 11726–11742   doi: 10.1093/nar/gky871​

  • Gao, F., and Simon, A.E.  2017.  Differential use of 3 ' CITEs by the subgenomic RNA of Pea enation mosaic virus 2.  Virology 510, 194-204.

  • Du, Z., Alekhina, O.M., Vassilenko, K.S., and Simon, A.E.  2017. Concerted action of two 3’ cap-independent translation enhancers increases the competitive strength of translated viral genomes.  Nucleic Acids Res.  doi: 10.1093/nar/gkx643   PMCID: PMC5766195

  • Le, M.-T., Kasprzak, W.K., Kim, T., Gao, F., Young, M.Y.L, Yuan, X., Shapiro, B.A., Seog, J., and Simon, A.E.  2017.  Combined single molecule experimental and computational approaches for understanding the unfolding pathway of a viral translation enhancer that participates in a conformational switch.  RNA Biol  DOI: 10.1080/15476286.2017.1325069  PMCID: PMC5785213

  • ​Le, M.-T., Kasprzak, W.K., Kim, T., Gao, F., Young, M.Y.L, Yuan, X., Shapiro, B.A., Seog, J., and Simon, A.E.  2017.  Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch.   eLife 6, e22883.   https://t.co/JwfvZSZOmd  PMCID: PMC5336357

  • May, J., Johnson, P., Saleen, H., and Simon, A.E. 2017.  A sequence-independent, unstructured IRES is responsible for internal expression of the coat protein of Turnip crinkle virus.  J Virol [SPOTLIGHT selection] 91, e02421.  DOI: 10.1128/JVI.02421-16    PMCID: PMC5375686

  • ​Le, M.-T., Brown, R. E., Longhini, A. P., Simon, A. E., and Dayie, T. K.  2015. In vivo, large-scale preparation of uniformly (15)N- and site-specifically (13)C-labeled homogeneous, recombinant RNA for NMR Studies.  Methods Enzymol 265, 495-535. DOI: 10.1016/bs.mie.2015.07.020

  • Chattopadhyay, M., Stupina, V.A., Gao, F., Szarko, C.R., Kuhlmann, M.M., Yuan, X., Shi, K., and Simon, A.E.  2015.  Requirement for host RNA silencing components and the virus silencing suppressor when second-site mutations compensate for structural defects in the 3’UTR.  J Virol 89, 11603-11618.  DOI: 10.1128/JVI.01566-15​

  • Simon, A.E.  2015.  3’UTR of carmoviruses.  Virus Res.  206, 27-36.  DOI: 10.1016/j.virusres.2015.01.023

  • ​Gao, F., Kasprzak, W, Szarko, C, Shapiro, BA, and Simon, AE.  2014.  The 3' untranslated region of Pea enation mosaic virus contains two T-shaped, ribosome-binding, cap-independent translation enhancers.  J Virol 88, 11696-11712.  PMCID: PMC4178710

  • Chattopadhyay, M., Kuhlmann, M., Kumar, K., and Simon, A.E.  2014.  Position of the kissing-loop interaction associated with PTE-type 3’CITEs can affect enhancement of cap-independent translation.  Virology  458-459, 43-52.  PMCID: PMC4101382

  • Gao, F., Reddy, S., Kasprzak, W., Shapiro, B.A., Dinman, J.D., and Simon, A.E.  2013. The kissing-loop T-shaped structure translational enhancer of Pea enation mosaic virus can bind simultaneously to ribosomes and a 5′ proximal hairpin.  J Virol 87, 11987-2002. PMCID: PMC3807929

  • Simon, A. E., and Miller, W. A.  2013.   3’ Cap-independent translation enhancers of plant viruses.  Annu Rev Microbiol 67: 21–42. PMCID: PMC4034384

  • Stupina, V.A. and Simon, A.E.  2013.   Preparation of biologically active Arabidopsis ribosomes and comparison with yeast ribosomes for binding to a tRNA-mimic that enhances translation of plant plus-strand RNA viruses. Front Plant Sci 4, 271. doi: 10.3389/fpls.2013.  PMCID: PMC3718319

  • Gao, F., Kasprzak, W., Stupina, V.A., Shapiro, B.A. and Simon, A.E.  2012.  A ribosome-binding, 3’ translational enhancer has a T-shaped structure and engages in a long distance RNA:RNA interaction.  J Virol 86, 9828-9842.  PMCID: PMC3446580

  • Yuan, X., Shi, K., and Simon, A.E.  2012.  An interactive network of RNA elements supports translation and replication in Turnip crinkle virus.  J Virol 86, 4065-4081.  PMCID: PMC3318645

  • Guo, R., Meskauskas, A., Dinman, J.D., and Simon, A.E.  2011.  Evolution of a helper virus-derived ribosome binding translational enhancer in an untranslated satellite RNA of Turnip crinkle virus.  Virology 419, 10-16.  PMCID: PMC3176665

  • Chattopadhyay, M., Shi, K., Yuan, X., and Simon, A.E.  2011.  Long-distance kissing loop interactions between a 3’ proximal Y-shaped structure and apical loops of 5’ hairpins enhance translation of Saguaro cactus virus.  Virology 417, 113-125.  PMCID: PMC3152624

  • Stupina, V.A, Yuan, X, Meskauskas, A., Dinman. J.D., and Simon, A.E.  2011.  Ribosome binding to a 5’ translational enhancer is altered in the presence of the 3’UTR in cap-independent translation of Turnip crinkle virus.  J Virol 85, 4638-4653.  PMCID: PMC3126203

  • Yuan, X., Shi, K., Young, M. Y. L., and Simon, A. E. 2010.  The terminal loop of a 3’ proximal hairpin plays a critical role in the structure of the 3’ region of Turnip crinkle virus and the RdRp-mediated conformational switch.  Virology 402, 271-280.  PMCID: PMC2891086  PMCID: PMC2803139

  • ​Yuan, X., Shi, K., Meskauskas, A. and Simon, A.E.  2009.  The 3’ end of Turnip crinkle virus contains a highly interactive structure with a translational enhancer that is disrupted by binding to the RNA-dependent RNA polymerase.  RNA 15, 1849-1864. PMCID: PMC2743042

  • ​Stupina, V. A., Meskauskas, A., McCormack, J. C., Yingling, Y. G., Kasprzak, W., Shapiro, B. A., Dinman, J. D., and Simon, A. E.  2008.  The 3' proximal translational enhancer of Turnip crinkle virus binds to 60S ribosomal subunits.  RNA 14, 2379-2393.  PMCID: PMC2578866

  • McCormack, J. C., Yuan, X., Yingling, Y. G., Zamora, R. E., Shapiro, B. A., and Simon, A. E.  2008.  Structural domains within the 3' UTR of Turnip crinkle virus.  J Virol 82, 8706-8720. PMCID: PMC2519621

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