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Structural basis for m7G recognition and 2′-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I

2016; National Academy of Sciences; Volume: 113; Issue: 3 Linguagem: Inglês

10.1073/pnas.1515152113

1091-6490

Swapnil C. Devarkar, Chen Wang, Matthew T. Miller, Anand Ramanathan, Fuguo Jiang, Abdul Ghafoor Khan, Smita S. Patel, Joseph Marcotrigiano,

Immune Response and Inflammation

Significance The cytosolic innate immune receptor Retinoic Acid Inducible Gene-I (RIG-I) is the principal detector of pathogenic RNAs carrying a 5′-triphosphate (5′ppp). Self RNAs like mRNAs evade recognition by RIG-I due to posttranscriptional modifications like 5′-end capping with 7-methyl guanosine (m7G) and 2′-O-methylation of 5′-end nucleotides. Viruses have also evolved mechanisms to mimic these modifications, which in part is believed to aid in immune evasion. Currently, it is unclear how these modifications modulate RIG-I recognition. This paper provides structural and mechanistic insights into the roles of the m7G cap and 2′-O-methylation in RIG-I evasion. We show that RIG-I accommodates the m7G base while maintaining the 5′ppp contacts and can recognize Cap-0 RNAs but not Cap-1.