Coding and non-coding RNAs, the frontier has never been so blurred

Abstract

In molecular biology, one of the founding dogmas states that genetic information, stored in the form of DNA molecules in the majority of living organisms, is translated into proteins via transient intermediaries, the RNAs. However, over the past 50 years, an increasing number of studies have highlighted that RNAs have a more significant and broader role. Whereas all the genomes of living organisms, whether single-cell or multi-cellular, have a high proportion of loci that are transcribed into RNA, this transcript is not necessarily translated into protein but can perform functions within the cell as the form of RNA. As a consequence, RNAs translated into proteins were named messenger RNAs (mRNA) as opposed to those that do not, which are referred to as non-coding or regulatory RNAs (ncRNA), clearly discriminating RNAs according to their protein coding capacity. Until recently, the coding/non-coding distinction appeared to be obvious, although it became more blurred in recent years. The first hints emerged when it became evident that the repertoire of genome-encoded RNAs is far more extensive and complex than previously thought. Indeed, many RNAs, here referred to as bifunctional RNAs (bifRNA), have both regulatory/non-coding and coding functions. The balance between non-coding and coding RNAs levels is modulated depending on the stage of development or differentiation, environmental cues, disturbances caused by a pathogen, etc. After having re-defined this striking but expanding class of bifRNAs, we will propose an estimate of the fraction of the human transcriptome that they may represent.