To cap it all off, again: dynamic capping and recapping of coding and non-coding RNAs to control transcript fate and biological activity

The addition of the methyl-7-guanosine (m(7)G) “cap” on the 5' ends of coding and some non-coding RNAs is essential for their protein coding capacity and biochemical activity, respectively. It was previously considered that capping was a constitutive process that generates a complete cap on all transcripts at steady-state. However, development of new methodologies demonstrated that steady-state capping is a dynamic and regulatable feature of many coding and non-coding RNAs. Indeed, capping status of specific RNAs can flux during differentiation and development, thereby impacting on their protein-coding capacity and activity. Moreover, in some primary cancer specimens, capping can be elevated for transcripts encoding proteins involved in proliferation and survival corresponding to their increased protein levels. Overexpression of one of the capping enzymes (RNMT), the transcription factor MYC or the eukaryotic translation initiation factor eIF4E all led to increased levels of steady-state capping of selected transcripts. Additionally, transcripts can be decapped and recapped, allowing these to be sequestered until needed. This review provides a summary of the major advances in enzymatic and affinity-based approaches to quantify m(7)G capping. Further, we summarize the evidence for regulation of capping. Capping has emerged as a significant regulatory step in RNA metabolism which is poised to impact a myriad of biological processes.