Post-transcriptional RNA-mediated regulation in infection: mechanisms, functions, and analytical approaches.

Abstract

Infectious pathogens extensively rewire host RNA processing, yet most studies examine individual processing mechanisms in isolation. In this review, we synthesize evidence that alternative splicing, N6-methyladenosine (m⁶A) methylation, and adenosine-to-inosine (A-to-I) RNA editing collectively shape infection outcomes across viral, bacterial, and parasitic pathogens by modulating host defense and pathogen replication. We highlight how pathogens hijack or are constrained by these mechanisms, with particular emphasis on underexplored bacterial and parasitic systems. We then propose a metatranscriptomics framework that integrates long-read and direct RNA sequencing with specialized computational tools to jointly profile splicing, m⁶A, and A-to-I editing in host and pathogen. Such integrative analyses will reveal convergent regulatory nodes and guide the development of host-directed therapies.