In “Hantavirus protein replaces eIF4F” we discussed how the binding of hantavirus N protein to the 5′-cap structure on mRNA replaces the translation complex eIF4F. A second research group has revealed yet another function for this interaction: the N protein sequesters mRNA caps in P bodies, for subsequent use during the initiation of viral mRNA synthesis.
The synthesis of mRNA in cells infected with members of three different viral families, bunyaviruses (to which hantaviruses belong), orthomyxoviruses, and arenaviruses is unusual because it is primed with a 5’capped oligonucleotide derived from cellular mRNAs. These capped primers are cleaved from cell mRNAs by viral endonucleases. After finding that the hantavirus N protein binds short, capped RNAs, the authors wondered whether such oligonucleotides might be stored in P bodies. These are regions of the cytoplasm that contain a variety of enzymes involved in turnover of mRNA; among other activities, they are storage areas for mRNAs that are not being translated into protein. The authors found that the hantavirus N protein localizes to P bodies, where it was associated with 5′-caps. The N protein-associated 5’caps, which were protected from degradation, were also used for viral mRNA synthesis.
Apparently these authors have also found that N protein can replace eIF4F during translation (although the data are not shown). They suggest that N protein remains bound to the 5′-cap structure during initiation of mRNA synthesis, and remains in place after the mRNA is complete. The protein is then in an excellent position to mediate ribosome binding to the mRNA. This model would imply that hantavirus mRNA translation is largely independent of the cap binding protein, eIF4E, a conclusion consistent with previous experimental results. A recent report indicates that influenza mRNA translation does not require eIF4E. Because influenza mRNA synthesis is also primed with capped oligonucleotides, the obvious – yet unproven – conclusion is that these caps are also stored in P bodies.
Thanks to Aidan for the title of this post.
Mir, M., Duran, W., Hjelle, B., Ye, C., & Panganiban, A. (2008). Storage of cellular 5′ mRNA caps in P bodies for viral cap-snatching Proceedings of the National Academy of Sciences, 105 (49), 19294-19299 DOI: 10.1073/pnas.0807211105