Directing RNA-modifying machineries towards endogenous RNAs: opportunities and challenges

Over 170 chemical modifications can be naturally installed on RNA, all of which are catalyzed by dedicated machineries. These modifications can alter RNA sequence structure, stability, and translation as well as serving as quality control marks that record aspects of RNA processing. The diverse roles played by RNAs within cells has motivated endeavors to exogenously introduce RNA modifications at target sites for diverse purposes ranging from recording RNA:protein interactions to therapeutic applications. Here, we discuss these applications and the approaches that have been employed to engineer RNA-modifying machineries, and highlight persisting challenges and perspectives.