Abstract
Significance Ribosomes decode genetic information encoded in mRNAs to synthesize cellular proteins. Initiation of translation is a key step, during which the ORF coding for a protein gets properly positioned on the ribosome with the AUG start codon and its cognate tRNA located in the ribosomal peptidyl site. Here, we report molecular structures of a eukaryotic ribosome complexed with viral mRNA, which uncover an unusual mechanism of initiation. The structures reveal that viral mRNAs carrying an intergenic RNA structure known as the internal ribosome entry site (IRES) initiate translation by binding a tRNA-mRNA–like element in the aminoacyl site of the ribosome. A structural mechanism of how viral mRNAs with intergenic IRESs hijack host ribosomes is proposed.
References
60
Referenced
61
-
WC Merrick, Cap-dependent and cap-independent translation in eukaryotic systems. Gene 332, 1–11 (2004).
(
10.1016/j.gene.2004.02.051
) / Gene / Cap-dependent and cap-independent translation in eukaryotic systems by Merrick WC (2004) -
TV Pestova, et al., Molecular mechanisms of translation initiation in eukaryotes. Proc Natl Acad Sci USA 98, 7029–7036 (2001).
(
10.1073/pnas.111145798
) / Proc Natl Acad Sci USA / Molecular mechanisms of translation initiation in eukaryotes by Pestova TV (2001) -
L Balvay, R Soto Rifo, EP Ricci, D Decimo, T Ohlmann, Structural and functional diversity of viral IRESes. Biochim Biophys Acta 1789, 542–557 (2009).
(
10.1016/j.bbagrm.2009.07.005
) / Biochim Biophys Acta / Structural and functional diversity of viral IRESes by Balvay L (2009) -
MI Hertz, SR Thompson, Mechanism of translation initiation by Dicistroviridae IGR IRESs. Virology 411, 355–361 (2011).
(
10.1016/j.virol.2011.01.005
) / Virology / Mechanism of translation initiation by Dicistroviridae IGR IRESs by Hertz MI (2011) -
CU Hellen, IRES-induced conformational changes in the ribosome and the mechanism of translation initiation by internal ribosomal entry. Biochim Biophys Acta 1789, 558–570 (2009).
(
10.1016/j.bbagrm.2009.06.001
) / Biochim Biophys Acta / IRES-induced conformational changes in the ribosome and the mechanism of translation initiation by internal ribosomal entry by Hellen CU (2009) -
E Jan, et al., Initiator Met-tRNA-independent translation mediated by an internal ribosome entry site element in cricket paralysis virus-like insect viruses. Cold Spring Harb Symp Quant Biol 66, 285–292 (2001).
(
10.1101/sqb.2001.66.285
) / Cold Spring Harb Symp Quant Biol / Initiator Met-tRNA-independent translation mediated by an internal ribosome entry site element in cricket paralysis virus-like insect viruses by Jan E (2001) -
JE Wilson, TV Pestova, CU Hellen, P Sarnow, Initiation of protein synthesis from the A site of the ribosome. Cell 102, 511–520 (2000).
(
10.1016/S0092-8674(00)00055-6
) / Cell / Initiation of protein synthesis from the A site of the ribosome by Wilson JE (2000) -
E Jan, P Sarnow, Factorless ribosome assembly on the internal ribosome entry site of cricket paralysis virus. J Mol Biol 324, 889–902 (2002).
(
10.1016/S0022-2836(02)01099-9
) / J Mol Biol / Factorless ribosome assembly on the internal ribosome entry site of cricket paralysis virus by Jan E (2002) -
T Nishiyama, et al., Structural elements in the internal ribosome entry site of Plautia stali intestine virus responsible for binding with ribosomes. Nucleic Acids Res 31, 2434–2442 (2003).
(
10.1093/nar/gkg336
) / Nucleic Acids Res / Structural elements in the internal ribosome entry site of Plautia stali intestine virus responsible for binding with ribosomes by Nishiyama T (2003) -
RC Cevallos, P Sarnow, Factor-independent assembly of elongation-competent ribosomes by an internal ribosome entry site located in an RNA virus that infects penaeid shrimp. J Virol 79, 677–683 (2005).
(
10.1128/JVI.79.2.677-683.2005
) / J Virol / Factor-independent assembly of elongation-competent ribosomes by an internal ribosome entry site located in an RNA virus that infects penaeid shrimp by Cevallos RC (2005) -
CW Hilbers, PJ Michiels, HA Heus, New developments in structure determination of pseudoknots. Biopolymers 48, 137–153 (1998).
(
10.1002/(SICI)1097-0282(1998)48:2<137::AID-BIP4>3.0.CO;2-H
) / Biopolymers / New developments in structure determination of pseudoknots by Hilbers CW (1998) -
JS Pfingsten, DA Costantino, JS Kieft, Structural basis for ribosome recruitment and manipulation by a viral IRES RNA. Science 314, 1450–1454 (2006).
(
10.1126/science.1133281
) / Science / Structural basis for ribosome recruitment and manipulation by a viral IRES RNA by Pfingsten JS (2006) -
JS Pfingsten, DA Costantino, JS Kieft, Conservation and diversity among the three-dimensional folds of the Dicistroviridae intergenic region IRESes. J Mol Biol 370, 856–869 (2007).
(
10.1016/j.jmb.2007.04.076
) / J Mol Biol / Conservation and diversity among the three-dimensional folds of the Dicistroviridae intergenic region IRESes by Pfingsten JS (2007) -
DA Costantino, JS Pfingsten, RP Rambo, JS Kieft, tRNA-mRNA mimicry drives translation initiation from a viral IRES. Nat Struct Mol Biol 15, 57–64 (2008).
(
10.1038/nsmb1351
) / Nat Struct Mol Biol / tRNA-mRNA mimicry drives translation initiation from a viral IRES by Costantino DA (2008) -
JS Kieft, Viral IRES RNA structures and ribosome interactions. Trends Biochem Sci 33, 274–283 (2008).
(
10.1016/j.tibs.2008.04.007
) / Trends Biochem Sci / Viral IRES RNA structures and ribosome interactions by Kieft JS (2008) -
J Zhu, et al., Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome. Proc Natl Acad Sci USA 108, 1839–1844 (2011).
(
10.1073/pnas.1018582108
) / Proc Natl Acad Sci USA / Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome by Zhu J (2011) -
E Jan, TG Kinzy, P Sarnow, Divergent tRNA-like element supports initiation, elongation, and termination of protein biosynthesis. Proc Natl Acad Sci USA 100, 15410–15415 (2003).
(
10.1073/pnas.2535183100
) / Proc Natl Acad Sci USA / Divergent tRNA-like element supports initiation, elongation, and termination of protein biosynthesis by Jan E (2003) -
CM Spahn, et al., Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor. Cell 118, 465–475 (2004).
(
10.1016/j.cell.2004.08.001
) / Cell / Cryo-EM visualization of a viral internal ribosome entry site bound to human ribosomes: The IRES functions as an RNA-based translation factor by Spahn CM (2004) -
M Schüler, et al., Structure of the ribosome-bound cricket paralysis virus IRES RNA. Nat Struct Mol Biol 13, 1092–1096 (2006).
(
10.1038/nsmb1177
) / Nat Struct Mol Biol / Structure of the ribosome-bound cricket paralysis virus IRES RNA by Schüler M (2006) -
DV Lightner, et al., Historic emergence, impact and current status of shrimp pathogens in the Americas. J Invertebr Pathol 110, 174–183 (2012).
(
10.1016/j.jip.2012.03.006
) / J Invertebr Pathol / Historic emergence, impact and current status of shrimp pathogens in the Americas by Lightner DV (2012) -
A Ben-Shem, et al., The structure of the eukaryotic ribosome at 3.0 Å resolution. Science 334, 1524–1529 (2011).
(
10.1126/science.1212642
) / Science / The structure of the eukaryotic ribosome at 3.0 Å resolution by Ben-Shem A (2011) -
H Yamamoto, N Nakashima, Y Ikeda, T Uchiumi, Binding mode of the first aminoacyl-tRNA in translation initiation mediated by Plautia stali intestine virus internal ribosome entry site. J Biol Chem 282, 7770–7776 (2007).
(
10.1074/jbc.M610887200
) / J Biol Chem / Binding mode of the first aminoacyl-tRNA in translation initiation mediated by Plautia stali intestine virus internal ribosome entry site by Yamamoto H (2007) -
TV Pestova, CU Hellen, Translation elongation after assembly of ribosomes on the Cricket paralysis virus internal ribosomal entry site without initiation factors or initiator tRNA. Genes Dev 17, 181–186 (2003).
(
10.1101/gad.1040803
) / Genes Dev / Translation elongation after assembly of ribosomes on the Cricket paralysis virus internal ribosomal entry site without initiation factors or initiator tRNA by Pestova TV (2003) -
RJ Jackson, CU Hellen, TV Pestova, The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11, 113–127 (2010).
(
10.1038/nrm2838
) / Nat Rev Mol Cell Biol / The mechanism of eukaryotic translation initiation and principles of its regulation by Jackson RJ (2010) -
P Sarnow, RC Cevallos, E Jan, Takeover of host ribosomes by divergent IRES elements. Biochem Soc Trans 33, 1479–1482 (2005).
(
10.1042/BST0331479
) / Biochem Soc Trans / Takeover of host ribosomes by divergent IRES elements by Sarnow P (2005) -
N Demeshkina, L Jenner, E Westhof, M Yusupov, G Yusupova, A new understanding of the decoding principle on the ribosome. Nature 484, 256–259 (2012).
(
10.1038/nature10913
) / Nature / A new understanding of the decoding principle on the ribosome by Demeshkina N (2012) -
JM Ogle, et al., Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science 292, 897–902 (2001).
(
10.1126/science.1060612
) / Science / Recognition of cognate transfer RNA by the 30S ribosomal subunit by Ogle JM (2001) -
M Selmer, et al., Structure of the 70S ribosome complexed with mRNA and tRNA. Science 313, 1935–1942 (2006).
(
10.1126/science.1131127
) / Science / Structure of the 70S ribosome complexed with mRNA and tRNA by Selmer M (2006) -
LB Jenner, N Demeshkina, G Yusupova, M Yusupov, Structural aspects of messenger RNA reading frame maintenance by the ribosome. Nat Struct Mol Biol 17, 555–560 (2010).
(
10.1038/nsmb.1790
) / Nat Struct Mol Biol / Structural aspects of messenger RNA reading frame maintenance by the ribosome by Jenner LB (2010) -
CJ Jang, E Jan, Modular domains of the Dicistroviridae intergenic internal ribosome entry site. RNA 16, 1182–1195 (2010).
(
10.1261/rna.2044610
) / RNA / Modular domains of the Dicistroviridae intergenic internal ribosome entry site by Jang CJ (2010) -
M Weisser, F Voigts-Hoffmann, J Rabl, M Leibundgut, N Ban, The crystal structure of the eukaryotic 40S ribosomal subunit in complex with eIF1 and eIF1A. Nat Struct Mol Biol 20, 1015–1017 (2013).
(
10.1038/nsmb.2622
) / Nat Struct Mol Biol / The crystal structure of the eukaryotic 40S ribosomal subunit in complex with eIF1 and eIF1A by Weisser M (2013) -
AP Carter, et al., Crystal structure of an initiation factor bound to the 30S ribosomal subunit. Science 291, 498–501 (2001).
(
10.1126/science.1057766
) / Science / Crystal structure of an initiation factor bound to the 30S ribosomal subunit by Carter AP (2001) -
AA Korostelev, Structural aspects of translation termination on the ribosome. RNA 17, 1409–1421 (2011).
(
10.1261/rna.2733411
) / RNA / Structural aspects of translation termination on the ribosome by Korostelev AA (2011) -
G Yusupova, L Jenner, B Rees, D Moras, M Yusupov, Structural basis for messenger RNA movement on the ribosome. Nature 444, 391–394 (2006).
(
10.1038/nature05281
) / Nature / Structural basis for messenger RNA movement on the ribosome by Yusupova G (2006) -
PV Cornish, et al., Following movement of the L1 stalk between three functional states in single ribosomes. Proc Natl Acad Sci USA 106, 2571–2576 (2009).
(
10.1073/pnas.0813180106
) / Proc Natl Acad Sci USA / Following movement of the L1 stalk between three functional states in single ribosomes by Cornish PV (2009) -
M Valle, et al., Locking and unlocking of ribosomal motions. Cell 114, 123–134 (2003).
(
10.1016/S0092-8674(03)00476-8
) / Cell / Locking and unlocking of ribosomal motions by Valle M (2003) -
J Fei, P Kosuri, DD MacDougall, RL Gonzalez, Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation. Mol Cell 30, 348–359 (2008).
(
10.1016/j.molcel.2008.03.012
) / Mol Cell / Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation by Fei J (2008) -
LH Horan, HF Noller, Intersubunit movement is required for ribosomal translocation. Proc Natl Acad Sci USA 104, 4881–4885 (2007).
(
10.1073/pnas.0700762104
) / Proc Natl Acad Sci USA / Intersubunit movement is required for ribosomal translocation by Horan LH (2007) -
X Agirrezabala, et al., Structural characterization of mRNA-tRNA translocation intermediates. Proc Natl Acad Sci USA 109, 6094–6099 (2012).
(
10.1073/pnas.1201288109
) / Proc Natl Acad Sci USA / Structural characterization of mRNA-tRNA translocation intermediates by Agirrezabala X (2012) -
J Frank, RK Agrawal, A ratchet-like inter-subunit reorganization of the ribosome during translocation. Nature 406, 318–322 (2000).
(
10.1038/35018597
) / Nature / A ratchet-like inter-subunit reorganization of the ribosome during translocation by Frank J (2000) -
DN Ermolenko, et al., Observation of intersubunit movement of the ribosome in solution using FRET. J Mol Biol 370, 530–540 (2007).
(
10.1016/j.jmb.2007.04.042
) / J Mol Biol / Observation of intersubunit movement of the ribosome in solution using FRET by Ermolenko DN (2007) -
X Agirrezabala, et al., Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome. Mol Cell 32, 190–197 (2008).
(
10.1016/j.molcel.2008.10.001
) / Mol Cell / Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome by Agirrezabala X (2008) -
P Julián, et al., Structure of ratcheted ribosomes with tRNAs in hybrid states. Proc Natl Acad Sci USA 105, 16924–16927 (2008).
(
10.1073/pnas.0809587105
) / Proc Natl Acad Sci USA / Structure of ratcheted ribosomes with tRNAs in hybrid states by Julián P (2008) -
T Budkevich, et al., Structure and dynamics of the mammalian ribosomal pretranslocation complex. Mol Cell 44, 214–224 (2011).
(
10.1016/j.molcel.2011.07.040
) / Mol Cell / Structure and dynamics of the mammalian ribosomal pretranslocation complex by Budkevich T (2011) -
D Moazed, HF Noller, Intermediate states in the movement of transfer RNA in the ribosome. Nature 342, 142–148 (1989).
(
10.1038/342142a0
) / Nature / Intermediate states in the movement of transfer RNA in the ribosome by Moazed D (1989) -
D Hartz, DS McPheeters, L Gold, Selection of the initiator tRNA by Escherichia coli initiation factors. Genes Dev 3, 1899–1912 (1989).
(
10.1101/gad.3.12a.1899
) / Genes Dev / Selection of the initiator tRNA by Escherichia coli initiation factors by Hartz D (1989) -
K Fredrick, HF Noller, Accurate translocation of mRNA by the ribosome requires a peptidyl group or its analog on the tRNA moving into the 30S P site. Mol Cell 9, 1125–1131 (2002).
(
10.1016/S1097-2765(02)00523-3
) / Mol Cell / Accurate translocation of mRNA by the ribosome requires a peptidyl group or its analog on the tRNA moving into the 30S P site by Fredrick K (2002) -
T Schneider-Poetsch, et al., Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol 6, 209–217 (2010).
(
10.1038/nchembio.304
) / Nat Chem Biol / Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin by Schneider-Poetsch T (2010) -
ME Filbin, BS Vollmar, D Shi, T Gonen, JS Kieft, HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation. Nat Struct Mol Biol 20, 150–158 (2013).
(
10.1038/nsmb.2465
) / Nat Struct Mol Biol / HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation by Filbin ME (2013) -
SE Dmitriev, AV Pisarev, MP Rubtsova, YE Dunaevsky, IN Shatsky, Conversion of 48S translation preinitiation complexes into 80S initiation complexes as revealed by toeprinting. FEBS Lett 533, 99–104 (2003).
(
10.1016/S0014-5793(02)03776-6
) / FEBS Lett / Conversion of 48S translation preinitiation complexes into 80S initiation complexes as revealed by toeprinting by Dmitriev SE (2003) -
L Chavatte, L Frolova, L Kisselev, A Favre, The polypeptide chain release factor eRF1 specifically contacts the s(4)UGA stop codon located in the A site of eukaryotic ribosomes. Eur J Biochem 268, 2896–2904 (2001).
(
10.1046/j.1432-1327.2001.02177.x
) / Eur J Biochem / The polypeptide chain release factor eRF1 specifically contacts the s(4)UGA stop codon located in the A site of eukaryotic ribosomes by Chavatte L (2001) -
D Taylor, et al., Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex. Proc Natl Acad Sci USA 109, 18413–18418 (2012).
(
10.1073/pnas.1216730109
) / Proc Natl Acad Sci USA / Cryo-EM structure of the mammalian eukaryotic release factor eRF1-eRF3-associated termination complex by Taylor D (2012) -
DN Ermolenko, HF Noller, mRNA translocation occurs during the second step of ribosomal intersubunit rotation. Nat Struct Mol Biol 18, 457–462 (2011).
(
10.1038/nsmb.2011
) / Nat Struct Mol Biol / mRNA translocation occurs during the second step of ribosomal intersubunit rotation by Ermolenko DN (2011) -
AF Brilot, AA Korostelev, DN Ermolenko, N Grigorieff, Structure of the ribosome with elongation factor G trapped in the pretranslocation state. Proc Natl Acad Sci USA 110, 20994–20999 (2013).
(
10.1073/pnas.1311423110
) / Proc Natl Acad Sci USA / Structure of the ribosome with elongation factor G trapped in the pretranslocation state by Brilot AF (2013) -
S Joseph, After the ribosome structure: How does translocation work? RNA 9, 160–164 (2003).
(
10.1261/rna.2163103
) / RNA / After the ribosome structure: How does translocation work? by Joseph S (2003) -
JS Feinberg, S Joseph, Identification of molecular interactions between P-site tRNA and the ribosome essential for translocation. Proc Natl Acad Sci USA 98, 11120–11125 (2001).
(
10.1073/pnas.211184098
) / Proc Natl Acad Sci USA / Identification of molecular interactions between P-site tRNA and the ribosome essential for translocation by Feinberg JS (2001) -
A Korostelev, S Trakhanov, M Laurberg, HF Noller, Crystal structure of a 70S ribosome-tRNA complex reveals functional interactions and rearrangements. Cell 126, 1065–1077 (2006).
(
10.1016/j.cell.2006.08.032
) / Cell / Crystal structure of a 70S ribosome-tRNA complex reveals functional interactions and rearrangements by Korostelev A (2006) -
IB Lomakin, NE Shirokikh, MM Yusupov, CU Hellen, TV Pestova, The fidelity of translation initiation: Reciprocal activities of eIF1, IF3 and YciH. EMBO J 25, 196–210 (2006).
(
10.1038/sj.emboj.7600904
) / EMBO J / The fidelity of translation initiation: Reciprocal activities of eIF1, IF3 and YciH by Lomakin IB (2006) -
LD Kapp, SE Kolitz, JR Lorsch, Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation. RNA 12, 751–764 (2006).
(
10.1261/rna.2263906
) / RNA / Yeast initiator tRNA identity elements cooperate to influence multiple steps of translation initiation by Kapp LD (2006) -
SR Starck, et al., Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science 336, 1719–1723 (2012).
(
10.1126/science.1220270
) / Science / Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I by Starck SR (2012)
Dates
Type | When |
---|---|
Created | 11 years, 2 months ago (June 10, 2014, 3:46 a.m.) |
Deposited | 3 years, 2 months ago (June 7, 2022, 7:29 a.m.) |
Indexed | 1 month, 2 weeks ago (July 2, 2025, 2:35 p.m.) |
Issued | 11 years, 2 months ago (June 9, 2014) |
Published | 11 years, 2 months ago (June 9, 2014) |
Published Online | 11 years, 2 months ago (June 9, 2014) |
Published Print | 11 years, 1 month ago (June 24, 2014) |
@article{Koh_2014, title={Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA–like structural element in the ribosomal decoding center}, volume={111}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1406335111}, DOI={10.1073/pnas.1406335111}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Koh, Cha San and Brilot, Axel F. and Grigorieff, Nikolaus and Korostelev, Andrei A.}, year={2014}, month=jun, pages={9139–9144} }