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Internal ribosome entry sites (IRES)

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Virology

Definition

Internal ribosome entry sites (IRES) are nucleotide sequences in viral RNA that allow for the direct recruitment of ribosomes to the mRNA for translation, bypassing the need for the traditional 5' cap structure. This feature is critical for the efficient expression of viral proteins, particularly under conditions where host cell translation initiation mechanisms are suppressed, such as during viral infection. IRES elements enable viruses to exploit host cellular machinery for their own replication and protein synthesis.

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5 Must Know Facts For Your Next Test

  1. IRES elements are commonly found in the genomes of many viruses, including picornaviruses and certain flaviviruses, allowing them to hijack the host's translational machinery.
  2. The presence of an IRES allows for cap-independent translation, enabling viral mRNA to be translated even when host cell cap-dependent translation is inhibited.
  3. IRES structures can vary significantly in their sequence and secondary structure, which influences their efficiency and specificity in ribosome recruitment.
  4. Some cellular mRNAs also contain IRES elements, highlighting a potential role for IRES-mediated translation in regulating gene expression during stress conditions.
  5. Understanding IRES mechanisms is crucial for developing antiviral strategies, as targeting these sites could inhibit viral protein synthesis.

Review Questions

  • How do internal ribosome entry sites (IRES) facilitate the translation of viral proteins during infection?
    • Internal ribosome entry sites (IRES) facilitate translation by allowing ribosomes to directly bind to the viral mRNA without the need for a 5' cap structure. This is particularly important during viral infection when host cell translation mechanisms may be compromised. By utilizing IRES elements, viruses can ensure their protein synthesis continues, even under conditions that typically inhibit host protein production, effectively allowing them to outcompete cellular messages.
  • Discuss the differences between cap-dependent translation and IRES-mediated translation in terms of initiation and context of use.
    • Cap-dependent translation involves the recognition of the 5' cap structure by ribosomes, requiring additional factors for efficient initiation. In contrast, IRES-mediated translation bypasses this requirement by directly recruiting ribosomes to specific sites on the viral mRNA. This mechanism is often utilized by viruses during stress or infection, where host cap-dependent pathways may be inhibited. Therefore, IRES elements provide a strategic advantage for viruses in hostile cellular environments.
  • Evaluate the implications of IRES usage by viruses for therapeutic development and antiviral strategies.
    • The usage of internal ribosome entry sites (IRES) by viruses presents unique opportunities and challenges for therapeutic development. By understanding how IRES elements function in recruiting ribosomes and facilitating protein synthesis, researchers can devise targeted antiviral strategies that inhibit this process. For instance, drugs that disrupt the structural integrity of IRES elements could effectively limit viral replication. Additionally, exploring IRES activity in cellular contexts may reveal new insights into regulating gene expression under stress, offering further avenues for therapeutic intervention.

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