RNA structure probing uncovers RNA structure-dependent biological functions

RNA molecules fold into complex structures that enable their diverse functions in cells. Recent revolutionary innovations in transcriptome-wide RNA structural probing of living cells have ushered in a new era in understanding RNA functions. Here, we summarize the latest technological advances for probing RNA secondary structures and discuss striking discoveries that have linked RNA regulation and biological processes through interrogation of RNA structures. In particular, we highlight how different long noncoding RNAs form into distinct secondary structures that determine their modes of interactions with protein partners to realize their unique functions. These dynamic structures mediate RNA regulatory functions through altering interactions with proteins and other RNAs. We also outline current methodological hurdles and speculate about future directions for development of the next generation of RNA structure-probing technologies of higher sensitivity and resolution, which could then be applied in increasingly physiologically relevant studies. This Review summarizes the recent technical advances in probing RNA secondary structures and discusses their connection with RNA regulatory functions in various biological processes and future directions in RNA structure-probing methods.