Colocalization of m6A and G-Quadruplex-FormingSequences in Viral RNA (HIV Zika Hepatitis B and SV40) SuggestsTopological Control of Adenosine N6-Methylation

摘要

This Outlook calls attention to two seemingly disparate and emerging fields regarding viral genomics that may be correlated in a way previously overlooked. First, we describe identification of conserved potential G-quadruplex-forming sequences (PQSs) in viral genomes relevant to human health. Studies have demonstrated that PQSs are highly conserved and can fold to G-quadruplexes (G4s) to regulate viral processes. Key examples include G4s as a countermeasure to the host’s immune system or G4-guided regulation of replication or transcription. Second, emerging data are discussed concerning the epitranscriptomic modification N⁶-methyladenosine (m⁶A) in viral RNA installed by host proteins in a consensus sequence favoring 5′-GG(m⁶A)C-3′. The proposed pathways by which m⁶A is written, read, and erased in viral RNA genomes and the impact this has on viral replication are described. The structural reason why certain sites are selected for modification while others are not is still mysterious. Finally, we discuss our new observations regarding these previous sequencing data that identifym⁶A installation within the loops of two-tetrad PQSs inthe RNA genomes of the Zika, HIV, hepatitis B, and SV40 viruses. Wehypothesize that conserved viral PQSs can provide a framework (sequenceand/or structural) for m⁶A installation. We also discussliterature sources suggesting that PQSs as sites of RNA modificationcould be a general phenomenon. We anticipate our observations willprovide ample opportunities for exciting discoveries regarding theinterplay between G4 structures and epitranscriptomic modificationsof RNA.