A protein that replaces the entire cellular eIF4F complex

Department of Molecular Genetics and Microbiology and the Center for Infectious Diseases & Immunity, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
The EMBO Journal (Impact Factor: 10.43). 11/2008; 27(23):3129-39. DOI: 10.1038/emboj.2008.228
Source: PubMed


The eIF4F cap-binding complex mediates the initiation of cellular mRNA translation. eIF4F is composed of eIF4E, which binds to the mRNA cap, eIF4G, which indirectly links the mRNA cap with the 43S pre-initiation complex, and eIF4A, which is a helicase necessary for initiation. Viral nucleocapsid proteins (N) function in both genome replication and RNA encapsidation. Surprisingly, we find that hantavirus N has multiple intrinsic activities that mimic and substitute for each of the three peptides of the cap-binding complex thereby enhancing the translation of viral mRNA. N binds with high affinity to the mRNA cap replacing eIF4E. N binds directly to the 43S pre-initiation complex facilitating loading of ribosomes onto capped mRNA functionally replacing eIF4G. Finally, N obviates the requirement for the helicase, eIF4A. The expression of a multifaceted viral protein that functionally supplants the cellular cap-binding complex is a unique strategy for viral mRNA translation initiation. The ability of N to directly mediate translation initiation would ensure the efficient translation of viral mRNA.

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    • "The N mRNA can be detected as early as 2 h post ANDV infection, and is the first viral RNA detected during infection [27], [28]. The N protein has several important roles in viral replication, as it encapsidates and protects viral RNA [29]–[31], and participates in initiating viral transcription and translation by binding cellular 5′ mRNA caps [32]. N protein gradient in the host cell cytoplasm also determines the switch from viral transcription to replication [33]. "
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    • "Interestingly, mRNAs carrying NMD signals were incorporated at an increased rate into Sin Nombre transcripts in human cells, and Sin Nombre N localizes with P bodies (Mir et al. 2008). This suggests potential conservation of decapping as antiviral against bunyaviruses in mammals. "
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    • "The hantavirus nucleoprotein binds to the cap of viral mRNAs with higher affinity than to cellular mRNAs, because of the presence of a short conserved sequence following the cap structure . The functions of eIF4A and eIF4G are also replaced by the hantavirus nucleoprotein (Mir and Panganiban, 2008). "
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