Fig. 3: Bifunctional ncRNAs exert non-coding functions and coding functions.

ncRNAs can be divided into two groups: housekeeping ncRNAs (upper panels) and regulatory ncRNAs (lower panels). Among housekeeping ncRNAs there are rRNAs, tRNAs, snRNAs and snoRNAs. Regulatory ncRNAs are further divided according to their length. Among short ncRNAs (< 200 nt) there are miRNAs (light blue). Long ncRNAs (lncRNAs, ≥ 500 nt) include lincRNAs (light green), pseudogenic RNAs (PGs, light gray), NATs (see Fig. 1c), and circRNAs (light purple). The primary function of miRNAs is non-coding (blue) and relates to post-transcriptional regulation of gene expression: mRNA degradation or translational repression mediated by the RISC complex. Among non-coding functions of lincRNAs there are: chromatin remodeling by epigenetic modification, transcription and splicing regulation, sponging of miRNAs and proteins, post-translational modification of proteins. Non-coding functions of PGs can be parental gene (PA)-related or unrelated. They include sponging of miRNAs and proteins, and mRNA degradation through endosiRNAs. S sense strand, AS antisense strand. circRNAs can be composed by only exons (EcircRNAs), both exons and introns (EIcircRNAs), or only introns (ciRNAs). They exert non-coding functions by acting as sponges for miRNAs and proteins, and by forming circRNPs that modulate signaling pathways. These groups of regulatory ncRNAs can all exert non-canonical coding functions as well, because they can be translated into ncPEPs, i.e., small peptides or proteins (orange).