Circuit logic: interdependent RNA modifications shape mRNA and noncoding RNA structure and function

Continued advances in high-throughput detection of posttranscriptional RNA modifications have enabled large-scale, mechanistic studies into the importance of RNA modifications in regulating the structure, function, and stability of coding and noncoding RNAs. More recently, this has expanded beyond investigations of independent single modifications, revealing the breadth of modification complexities in single transcripts and the biogenesis pathways involved that lead to coordinately modified RNA species. This has resulted in the concept of modification circuits, where one modification can promote or inhibit the subsequent installation of other modifications, or when modifications are coordinated across different RNA species. These circuits play important roles in the biogenesis of multistepped posttranscriptional modifications, modulate ribonucleoprotein complex formation and conformational switches, and mediate codon-biased translation through the coordination of mRNA and tRNA modifications. Here, I review evidence of complex modification circuits in mRNA and noncoding RNA and highlight open questions concerning the molecular mechanisms giving rise to modification circuits and their importance in the context of RNA processing and maturation.