Pervasive transcriptome interactions of protein-targeted drugs.

ABSTRACT: The off-target toxicity of drugs targeted to proteins imparts substantial health and economic costs. Proteome interaction studies can reveal off-target effects with unintended proteins; however, little attention has been paid to intracellular RNAs as potential off-targets that may contribute to toxicity. To begin to assess this, we developed a reactivity-based RNA profiling methodology and applied it to uncover transcriptome interactions of a set of Food and Drug Administration-approved small-molecule drugs in vivo. We show that these protein-targeted drugs pervasively interact with the human transcriptome and can exert unintended biological effects on RNA functions. In addition, we show that many off-target interactions occur at RNA loci associated with protein binding and structural chan

SUBMITTER: Fang L 

PROVIDER: S-EPMC12874518 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature