Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA.

O touro fica: anotações sobre 'O Testamento de Dom Quixote'

'O Testamento de Dom Quixote', 'script' by Glauber Rocha, is supposed to be loosely inspired in the last chapter of Cervantes' novel, although it is absolutely different from it: in the film the character doesn't recover his lucidity, but he lives surrounded by mystical delirium. Already in its first pages, it is obvious that it is a first draft of 'Cutting Heads', the film he shot in Spain in 1970, in spite of being completely different from the final movie. The comparison between both works allows us to see to what extent this essential seed was a forgotten one: the film was always publicised as a version of 'Macbeth', a reference which is missing here, and the 'Quijote' was never considered a point of depart, although its work with reality and dream determined the tone of the film from the very beginning.