The emerging biology of RNA post-transcriptional modifications

Abstract

RNA modifications have long been known to be central in the proper function of tRNA and rRNA. While chemical modifications in mRNA were discovered decades ago, their function has remained largely mysterious until recently. Using enrichment strategies coupled to next generation sequencing, multiple modifications have now been mapped on a transcriptome-wide scale in a variety of contexts. We now know that RNA modifications influence cell biology by many different mechanisms - by influencing RNA structure, by tuning interactions within the ribosome, and by recruiting specific binding proteins that intersect with other signaling pathways. They are also dynamic, changing in distribution or level in response to stresses such as heat shock and nutrient deprivation. Here, we provide an overview of recent themes that have emerged from the substantial progress that has been made in our understanding of chemical modifications across many major RNA classes in eukaryotes.

Keywords: Epitranscriptome; RNA modification; gene expression; post-transcriptional regulation; protein translation.

Figure 1.

Chemical structures of RNA modifications currently characterized in mRNA, schematized with their reported localization along transcripts. m⁶A has known functional roles at both the 5′UTR and the 3′UTR, regulating mRNA translation and decay, respectively. m¹A is localized primarily in the 5′UTR and early coding sequence, m⁵C is found primarily in untranslated regions, and Ψ is distributed throughout protein coding sequences, but their functions remain mysterious. While 2′OMe has been detected in mRNA samples, its distribution in the transcriptome has not yet been mapped.