Taking advantage of host cellular machinery

Original Article:
Jha, S. et al. Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase. Nature 546,651–655 (2017).

This is a story about how poxvirus turns human translation machinery in favor of viral transcript by modifying a ribosome-associated gene, RACK1. With the phosphorylation of RACK1, human ribosomes become fond of the uncapped transcripts with poly-adenylation in its 5’ untranslated region from poxvirus.

This might not look like the most intriguing story, and I did not think so either. Nevertheless, when I read the story incidentally, there are quite a few things that catch my interest.

Jha et al. found RACK1 promotes viral protein synthesis by comparing RACK1 knock-out cell to wild type, but they failed to over-express RACK1, and knocking down RACK1 failed repeat the observation despite decreased expression of RACK1. When I read this part, I longed for the motivation that kept the authors moving on. If I were in their shoes, I might get so haunted by the thought that it was some subtle technical errors preventing adequate over-expression or knock-down, and I would not discover how strictly the protein level of RACK1 is regulated that over-expression causes the degradation of both exogenous and endogenous RACK1 so the total amount remain the same, or how poxvirus only utilized a minor fraction of RACK1, so there was still enough after knocking it down.

The authors applied an uncommon montage here. Instead of explaining each transition so the story looks like an expedition, they chose to demonstrate the results one by one, and rationales, if present, were kept minimal and described with interpretation.

They started from how RACK1 could be post-translationally modified and then directly introduced PKCßII, a human gene played an important role in RACK1 phosphorylation, while emphasizing this phosphorylation is only seen in infected cells but never occurs in normal condition, which implicitly indicates it could not be the normal function of PKCßII to catalyze this phosphorylation on RACK1.

This montage is present through the article, creating a riddle-solving atmosphere.

The localization of RACK1 to “viral factory” was shown first and then the introduction to what viral factory is and their interpretation of the phenomena came together at the end of the paragraph.

It seems to be known that CAA repeat in the 5’ UTR of tobacco mosaic viral RNA is key to the preference of plant ribosome to viral transcripts, but the analogy of the poly-adenylated 5’ UTR of poxviral transcript to the CAA repeat-containing tobacco mosaic viral transcripts was only mentioned in the end.

Retrospectively speaking, it might be a good way to improve perceived impact — what the authors reported was a novel phenomenon, which is not intuitively linked to the strategy tobacco mosaic virus has been using. Perhaps this is an advanced writing style that I am not familiar with. After all, the montage creates an impression that the authors characterized a novel strategy and then found out this strategy is widely implemented in across kingdoms, while avoiding a narrative opening with “the strategy we find in poxvirus is reminiscent of a clever thing tobacco mosaic virus does”, which is an unfavorable alternative because it tastes like that the authors described yet another viral species that use a well-known strategy.