Eukaryotic translation initiation factor 4E availability controls the switch between cap-dependent and internal...

Area of Science:

• Molecular Biology
• Virology
• Biochemistry

Background:

• Cellular mRNA translation typically initiates via the m7G cap structure, involving the eukaryotic translation initiation factor 4F (eIF4F) complex.
• Internal ribosomal entry sites (IRESs) allow for cap-independent translation initiation, particularly utilized by viral mRNAs.
• The balance between cap-dependent and IRES-mediated translation is crucial for cellular and viral gene expression.

Purpose of the Study:

• To investigate the role of eIF4E availability in regulating the switch between cap-dependent and IRES-mediated translation.
• To elucidate the mechanism by which picornaviruses preferentially hijack host cell translation machinery during infection.

Main Methods:

• Utilized in vitro translation assays with varying concentrations of capped and IRES-containing mRNAs.
• Manipulated eIF4E availability within translation extracts.
• Analyzed the impact of eIF4E levels on the translation efficiency of both capped and IRES-driven mRNAs.

Main Results:

• A decrease in eIF4E availability significantly increased IRES-mediated viral mRNA translation when both capped and IRES mRNAs were present.
• This effect was not observed in extracts lacking capped mRNAs, highlighting competition for translation resources.
• Capped cellular mRNAs compete with viral IRES-containing mRNAs for limiting translation initiation factors like eIF4E.

Conclusions:

• eIF4E availability is a critical determinant in switching translation from cap-dependent to IRES-mediated pathways.
• Picornavirus infection likely exploits reduced eIF4E levels to promote viral mRNA translation over host mRNA translation.
• This mechanism explains the preferential translation of viral mRNAs observed during picornavirus infections.