Terminus-Associated Non-coding RNAs: Trash or Treasure?

3′ untranslated regions (3′ UTRs) of protein-coding genes are well known for their important roles in determining the fate of mRNAs in diverse processes, including trafficking, stabilization, translation, and RNA–protein interactions. However, non-coding RNAs (ncRNAs) scattered around 3′ termini of the protein-coding genes, here referred to as terminus-associated non-coding RNAs (TANRs), have not attracted wide attention in RNA research. Indeed, whether TANRs are transcriptional noise, degraded mRNA products, alternative 3′ UTRs, or functional molecules has remained unclear for a long time. As a new category of ncRNAs, TANRs are widespread, abundant, and conserved in diverse eukaryotes. The biogenesis of TANRs mainly follows the same promoter model, the RNA-dependent RNA polymerase activity-dependent model, or the independent promoter model. Functional studies of TANRs suggested that they are significantly involved in the versatile regulation of gene expression. For instance, at the transcriptional level, they can lead to transcriptional interference, induce the formation of gene loops, and participate in transcriptional termination. Furthermore, at the posttranscriptional level, they can act as microRNA sponges, and guide cleavage or modification of target RNAs. Here, we review current knowledge of the potential role of TANRs in the modulation of gene expression. In this review, we comprehensively summarize the current state of knowledge about TANRs, and discuss TANR nomenclature, relation to ncRNAs, cross-talk biogenesis pathways and potential functions. We further outline directions of future studies of TANRs, to promote investigations of this emerging and enigmatic category of RNA.