scholarly journals Dissemination of Internal Ribosomal Entry Sites (IRES) Between Viruses by Horizontal Gene Transfer

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 612
Author(s):  
Yani Arhab ◽  
Alexander G. Bulakhov ◽  
Tatyana V. Pestova ◽  
Christopher U.T. Hellen
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Viral Evolution ◽  
Internal Ribosomal Entry Site ◽  
Type I ◽  
Cell Type Specificity ◽  
Entry Site ◽  
Type Iv ◽  
Initiation Of Translation ◽  
Ribosomal Entry

Members of Picornaviridae and of the Hepacivirus, Pegivirus and Pestivirus genera of Flaviviridae all contain an internal ribosomal entry site (IRES) in the 5′-untranslated region (5′UTR) of their genomes. Each class of IRES has a conserved structure and promotes 5′-end-independent initiation of translation by a different mechanism. Picornavirus 5′UTRs, including the IRES, evolve independently of other parts of the genome and can move between genomes, most commonly by intratypic recombination. We review accumulating evidence that IRESs are genetic entities that can also move between members of different genera and even between families. Type IV IRESs, first identified in the Hepacivirus genus, have subsequently been identified in over 25 genera of Picornaviridae, juxtaposed against diverse coding sequences. In several genera, members have either type IV IRES or an IRES of type I, II or III. Similarly, in the genus Pegivirus, members contain either a type IV IRES or an unrelated type; both classes of IRES also occur in members of the genus Hepacivirus. IRESs utilize different mechanisms, have different factor requirements and contain determinants of viral growth, pathogenesis and cell type specificity. Their dissemination between viruses by horizontal gene transfer has unexpectedly emerged as an important facet of viral evolution.

scholarly journals Structural characterization of ribosome recruitment and translocation by type IV IRES

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jason Murray ◽  
Christos G Savva ◽  
Byung-Sik Shin ◽  
Thomas E Dever ◽  
V Ramakrishnan ◽  
...  
Keyword(s):  
Internal Ribosomal Entry Site ◽  
Ribosomal Subunit ◽  
Elongation Factor ◽  
Post Translational Modification ◽  
Entry Site ◽  
Small Ribosomal Subunit ◽  
Initiation Factors ◽  
Type Iv ◽  
Peptidyl Transfer ◽  
Initiation Of Translation

Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts the otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (<xref ref-type="bibr" rid="bib19">Fernández et al., 2014</xref>; <xref ref-type="bibr" rid="bib34">Koh et al., 2014</xref>), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation.

scholarly journals Metagenomic Discovery of CRISPR-Associated Transposons

2021 ◽  
Author(s):  
James R. Rybarski ◽  
Kuang Hu ◽  
Alexis M. Hill ◽  
Claus O. Wilke ◽  
Ilya J. Finkelstein
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Gene Editing ◽  
Type I ◽  
Genomic Databases ◽  
Type Iv ◽  
Cas Genes ◽  
Shed Light

AbstractCRISPR-associated transposons (CASTs) co-opt Cas genes for RNA-guided transposition. CASTs are exceedingly rare in genomic databases; recent surveys have reported Tn7-like transposons that co-opt Type I-F, I-B, and V-K CRISPR effectors. Here, we expand the diversity of reported CAST systems via a bioinformatic search of metagenomic databases. We discover new architectures for all known CASTs, including novel arrangements of the Cascade effectors, new self-targeting modalities, and minimal V-K systems. We also describe new families of CASTs that have co-opted the Type I-C and Type IV CRISPR-Cas systems. Our search for non-Tn7 CASTs identifies putative candidates that co-opt Cas12a for horizontal gene transfer. These new systems shed light on how CRISPR systems have co-evolved with transposases and expand the programmable gene editing toolkit.

scholarly journals Physical Association of Eukaryotic Initiation Factor 4G (eIF4G) with eIF4A Strongly Enhances Binding of eIF4G to the Internal Ribosomal Entry Site of Encephalomyocarditis Virus and Is Required for Internal Initiation of Translation

2000 ◽  
Vol 20 (16) ◽  
pp. 6019-6029 ◽  
Author(s):  
Ivan B. Lomakin ◽  
Christopher U. T. Hellen ◽  
Tatyana V. Pestova
Keyword(s):  
Complex Formation ◽  
Internal Ribosomal Entry Site ◽  
Encephalomyocarditis Virus ◽  
Initiation Factor ◽  
Rna Recognition Motif ◽  
Eukaryotic Initiation Factor ◽  
Entry Site ◽  
Amino Terminal ◽  
Initiation Of Translation ◽  
Ribosomal Entry

ABSTRACT Mammalian eukaryotic initiation factor 4GI (eIF4GI) may be divided into three similarly sized regions. The central region (amino acids [aa] 613 to 1090) binds eIF3, eIF4A, and the encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES) and mediates initiation on this RNA. We identified the regions of eIF4GI that are responsible for its specific interaction with the IRES and that are required to mediate 48S complex formation on the IRES in vitro. Mutational analysis demarcated the IRES binding fragment of eIF4GI (aa 746 to 949) and indicated that it does not resemble an RNA recognition motif (RRM)-like domain. An additional amino-terminal sequence (aa 722 to 746) was required for binding eIF4A and for 48S complex formation. eIF4GI bound the EMCV IRES and β-globin mRNA with similar affinities, but association with eIF4A increased its affinity for the EMCV IRES (but not β-globin RNA) by 2 orders of magnitude. On the other hand, eIF4GI mutants with defects in binding eIF4A were defective in mediating 48S complex formation even if they bound the IRES normally. These data indicate that the eIF4G-eIF4A complex, rather than eIF4G alone, is required for specific high-affinity binding to the EMCV IRES and for internal ribosomal entry on this RNA.

scholarly journals Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry.

1996 ◽  
Vol 16 (12) ◽  
pp. 6859-6869 ◽  
Author(s):  
T V Pestova ◽  
C U Hellen ◽  
I N Shatsky
Keyword(s):  
Internal Ribosomal Entry Site ◽  
Encephalomyocarditis Virus ◽  
Initiation Factor ◽  
Entry Site ◽  
Independent Manner ◽  
Initiation Factors ◽  
Virus Rna ◽  
Initiation Of Translation ◽  
Initiation Factor 2 ◽  
Ribosomal Entry

Translation of picornavirus RNA is initiated after ribosomal binding to an internal ribosomal entry site (IRES) within the 5' untranslated region. We have reconstituted IRES-mediated initiation on encephalomyocarditis virus RNA from purified components and used primer extension analysis to confirm the fidelity of 48S preinitiation complex formation. Eukaryotic initiation factor 2 (eIF2), eIF3, and eIF4F were required for initiation; eIF4B and to a lesser extent the pyrimidine tract-binding protein stimulated this process. We show that eIF4F binds to the IRES in a novel cap-independent manner and suggest that cap- and IRES-dependent initiation mechanisms utilize different modes of interaction with this factor to promote ribosomal attachment to mRNA.

scholarly journals CRISPR-Cas13a mediated targeting of hepatitis C virus internal-ribosomal entry site (IRES) as an effective antiviral strategy

2021 ◽  
Vol 136 ◽  
pp. 111239
Author(s):  
Muhammad Usman Ashraf ◽  
Hafiz Muhammad Salman ◽  
Muhammad Farhan Khalid ◽  
Muhammad Haider Farooq Khan ◽  
Saima Anwar ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Internal Ribosomal Entry Site ◽  
Entry Site ◽  
Ribosomal Entry

scholarly journals Riboproteomics of the Hepatitis C Virus Internal Ribosomal Entry Site

2004 ◽  
Vol 3 (5) ◽  
pp. 949-957 ◽  
Author(s):  
Henry Lu ◽  
Weiqun Li ◽  
William Stafford Noble ◽  
Donald Payan ◽  
D. C. Anderson
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Internal Ribosomal Entry Site ◽  
Entry Site ◽  
Ribosomal Entry

scholarly journals An internal ribosomal entry site mediates redox-sensitive translation of Nrf2

2009 ◽  
Vol 38 (3) ◽  
pp. 778-788 ◽  
Author(s):  
Wenge Li ◽  
Nehal Thakor ◽  
Eugenia Y. Xu ◽  
Ying Huang ◽  
Chi Chen ◽  
...  
Keyword(s):  
Internal Ribosomal Entry Site ◽  
Entry Site ◽  
Ribosomal Entry
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