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TitleStructural insights into the recruitment of viral type 2 IRES to ribosomal preinitiation complex for protein synthesis.
Journal, issue, pagesElife, Vol. 14, Year 2026
Publish dateJun 25, 2026
AuthorsDeepakash Das / Tanweer Hussain /
PubMed AbstractPicornaviruses employ internal ribosome entry sites (IRESs) in their genomic RNA to hijack the host's translational machinery. The picornavirus, encephalomyocarditis virus, employs a type 2 IRES ...Picornaviruses employ internal ribosome entry sites (IRESs) in their genomic RNA to hijack the host's translational machinery. The picornavirus, encephalomyocarditis virus, employs a type 2 IRES present in its 5' untranslated region (5'UTR) and requires 43S ribosomal preinitiation complex (PIC), the central domain of eukaryotic initiation factor (eIF) 4G, eIF4A, and an essential ITAF (IRES trans-acting factor)-polypyrimidine tract binding protein 1 (PTB1) to form 48S PIC. In this study, we have used cryo-electron microscopy (cryo-EM) to determine the structure of encephalomyocarditis virus (EMCV) IRES-bound mammalian 48S PIC in a scanning-arrested closed state at the start codon. The EMCV IRES domains contact initiator tRNA (tRNA) and 40S head at the inter-subunit interface, which reveals an altogether unique mechanism used by viruses to capture host translational machinery for its protein synthesis. The tRNA is held away from the 40S body in contrast to canonical cap-dependent translation while the domain I apical region of EMCV IRES mimics 28S rRNA of 60S to interact with 40S ribosomal head proteins uS13 and uS19. The structural analysis accounts for numerous previously reported biochemical studies on type 2 IRES and shows how type 2 IRES interacts with 43S PIC to form 48S PIC. This study provides mechanistic insights for understanding EMCV IRES-mediated translation initiation, which could be extrapolated to other IRESs sharing similar motifs and factor requirements, including type 1 viral IRESs.
External linksElife / PubMed:42345371 / PubMed Central
MethodsEM (single particle)
Resolution4.5 - 5.01 Å
Structure data

64644

9uzk

EMDB-64644, PDB-9uzk:
EMCV IRES captured on mammalian 40S with initiator tRNA
Method: EM (single particle) / Resolution: 4.6 Å

64645

9uzl

EMDB-64645, PDB-9uzl:
EMCV IRES captured on mammalian 40S ribosome with initiator tRNA and eIF2
Method: EM (single particle) / Resolution: 5.01 Å

64646

9uzm

EMDB-64646, PDB-9uzm:
40S ribosome without initiation factors
Method: EM (single particle) / Resolution: 4.5 Å

Source
  • oryctolagus cuniculus (rabbit)
  • encephalomyocarditis virus
KeywordsRIBOSOME / EMCV IRES / 40S ribosome / 48S PIC

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