Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome

Zhu, Jianyu; Коростелев, А.A.; Costantino, David A.; Donohue, John P.; Noller, Harry F.; Kieft, Jeffrey S.

doi:10.1073/pnas.1018582108

Cited by 44 publications

(60 citation statements)

References 52 publications

(77 reference statements)

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“…X-ray crystal structures of an isolated PKI fragment of the CrPV IRES suggested that PKI positions itself in the P site of the ribosome [47,55]. As mentioned above, the low-resolution cryo-EM structure of the 80S-bound CrPV IRES placed PKI near the P site [28].…”

Section: (A) Mechanism Of Crpv Ires Initiationmentioning

confidence: 94%

“…Early biochemical and structural data suggested that PKI is positioned in the P site of 80S : IRES initiation where it adopts a conformation that mimics P-site tRNA, while the Ala codon is subsequently positioned in the decoding centre (of the A site) of the ribosome [14,28,30,31,41,47]. However, recent studies have revealed that PKI of the IRES initially occupies the ribosomal A site, blocking tRNA binding [46,48].…”

Section: (A) Mechanism Of Crpv Ires Initiationmentioning

confidence: 99%

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Dynamics of IRES-mediated translation

Johnson

Grosely

Petrov

et al. 2017

Phil. Trans. R. Soc. B

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One contribution of 12 to a theme issue 'Perspectives on the ribosome'. Viral internal ribosome entry sites (IRESs) are unique RNA elements, which use stable and dynamic RNA structures to recruit ribosomes and drive protein synthesis. IRESs overcome the high complexity of the canonical eukaryotic translation initiation pathway, often functioning with a limited set of eukaryotic initiation factors. The simplest types of IRESs are typified by the cricket paralysis virus intergenic region (CrPV IGR) and hepatitis C virus (HCV) IRESs, both of which independently form high-affinity complexes with the small (40S) ribosomal subunit and bypass the molecular processes of cap-binding and scanning. Owing to their simplicity and ribosomal affinity, the CrPV and HCV IRES have been important models for structural and functional studies of the eukaryotic ribosome during initiation, serving as excellent targets for recent technological breakthroughs in cryogenic electron microscopy (cryo-EM) and single-molecule analysis. High-resolution structural models of ribosome : IRES complexes, coupled with dynamics studies, have clarified decades of biochemical research and provided an outline of the conformational and compositional trajectory of the ribosome during initiation. Here we review recent progress in the study of HCV-and CrPV-type IRESs, highlighting important structural and dynamics insights and the synergy between cryo-EM and single-molecule studies.This article is part of the themed issue 'Perspectives on the ribosome'.

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Section: (A) Mechanism Of Crpv Ires Initiationmentioning

confidence: 94%

Section: (A) Mechanism Of Crpv Ires Initiationmentioning

confidence: 99%

Dynamics of IRES-mediated translation

Johnson

Grosely

Petrov

et al. 2017

Phil. Trans. R. Soc. B

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“…In Dicistroviridae viruses (Costantino et al 2008;Zhu et al 2011), tRNA mimicry is critical for internal ribosome entry site (IRES) function. Although many retroviruses contain an IRES (Balvay et al 2009), the presence of an IRES in HIV-1 is somewhat controversial (Miele et al 1996;Brasey et al 2003) as the IRES appears to be active only under certain physiological conditions, such as G2/M arrest (Brasey et al 2003) or stress (Gendron et al 2011), and there is also evidence that ribosomal scanning occurs in part of the 5 ′ UTR (Berkhout et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Molecular mimicry of human tRNA^Lys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing

Jones

Saadatmand

Kleiman

et al. 2012

RNA

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The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA Lys3. Host cell tRNA Lys is selectively packaged into HIV-1 through a specific interaction between the major tRNA Lys -binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primerbinding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA Lys3 is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA Lys and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA Lys3 in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA Lys to increase the efficiency of tRNA Lys3 annealing to viral RNA.

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“…The crystal structure of an isolated PKI of the CrPV IGR IRES shows that the pseudoknot resembles the anticodon stem loop of tRNA bound to a cognate mRNA codon (14,15). Isolated PKI of CrPV and PSIV IRESs binds to the P site of the bacterial 70S ribosome, demonstrating that PKI has an affinity to the highly conserved tRNA binding sites on the ribosome (16).…”

mentioning

confidence: 99%

Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA–like structural element in the ribosomal decoding center

Koh

Brilot

Grigorieff

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

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In cap-dependent translation initiation, the open reading frame (ORF) of mRNA is established by the placement of the AUG start codon and initiator tRNA in the ribosomal peptidyl (P) site. Internal ribosome entry sites (IRESs) promote translation of mRNAs in a capindependent manner. We report two structures of the ribosomebound Taura syndrome virus (TSV) IRES belonging to the family of Dicistroviridae intergenic IRESs. Intersubunit rotational states differ in these structures, suggesting that ribosome dynamics play a role in IRES translocation. Pseudoknot I of the IRES occupies the ribosomal decoding center at the aminoacyl (A) site in a manner resembling that of the tRNA anticodon-mRNA codon. The structures reveal that the TSV IRES initiates translation by a previously unseen mechanism, which is conceptually distinct from initiator tRNA-dependent mechanisms. Specifically, the ORF of the IRES-driven mRNA is established by the placement of the preceding tRNA-mRNA-like structure in the A site, whereas the 40S P site remains unoccupied during this initial step.tRNA-mRNA mimicry | IRES-dependent initiation | factor-independent initiation | FREALIGN | real-space refinement

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Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome

Cited by 44 publications

References 52 publications

Dynamics of IRES-mediated translation

Dynamics of IRES-mediated translation

Molecular mimicry of human tRNA^Lys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing

Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA–like structural element in the ribosomal decoding center

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Crystal structures of complexes containing domains from two viral internal ribosome entry site (IRES) RNAs bound to the 70S ribosome

Cited by 44 publications

References 52 publications

Dynamics of IRES-mediated translation

Dynamics of IRES-mediated translation

Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing

Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA–like structural element in the ribosomal decoding center

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Molecular mimicry of human tRNA^Lys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing