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 (m7G) "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 m7G 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.

The eukaryotic translation initiation factor eIF4E is a direct transcriptional target of NF-κB and is aberrantly regulated in acute myeloid leukemia.

The eukaryotic translation initiation factor eIF4E is a potent oncogene elevated in many cancers, including the M4 and M5 subtypes of acute myeloid leukemia (AML). Although eIF4E RNA levels are elevated 3- to 10-fold in M4/M5 AML, the molecular underpinnings of this dysregulation were unknown. Here, we demonstrate that EIF4E is a direct transcriptional target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) that is dysregulated preferentially in M4 and M5 AML. In primary hematopoietic cells and in cell lines, eIF4E levels are induced by NF-κB activating stimuli. Pharmacological or genetic inhibition of NF-κB represses this activation. The endogenous human EIF4E promoter recruits p65 and cRel to evolutionarily conserved κB sites in vitro and in vivo following NF-κB activation. Transcriptional activation is demonstrated by recruitment of p300 to the κB sites and phosphorylated Pol II to the coding region. In primary AML specimens, generally we observe that substantially more NF-κB complexes associate with eIF4E promoter elements in M4 and M5 AML specimens examined than in other subtypes or unstimulated normal primary hematopoietic cells. Consistently, genetic inhibition of NF-κB abrogates eIF4E RNA levels in this same population. These findings provide novel insights into the transcriptional control of eIF4E and a novel molecular basis for its dysregulation in at least a subset of M4/M5 AML specimens.