The “guiding” principles of noncoding RNA function

Abstract The human genome is pervasively transcribed and yet only a small fraction of these RNAs (less than 2%) are known to code for proteins. The vast majority of the RNAs are classified as noncoding RNAs (ncRNAs) and are further subgrouped as small (shorter than 200 bases) and long noncoding RNAs. The ncRNAs have been identified in all three domains of life and regulate diverse cellular processes through transcriptional and posttranscriptional gene regulation. Most of these RNAs work in conjunction with proteins forming a wide array of base pairing interactions. The determinants of these base pairing interactions are now becoming more evident and show striking similarities among the diverse group of ncRNAs. Here we present a mechanistic overview of pairing between RNA–RNA or RNA–DNA that dictates the function of ncRNAs; we provide examples to illustrate that ncRNAs work through shared evolutionary mechanisms that encompasses a guide–target interaction, involving not only classical Watson–Crick but also noncanonical Wobble and Hoogsteen base pairing. We also highlight the similarities in target selection, proofreading, and the ruler mechanism of ncRNA–protein complexes that confers target specificity and target site selection. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA‐Based Catalysis > RNA‐Mediated Cleavage RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution