mRNA capping: biological functions and applications

Abstract

The 5′ m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2′O methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed. We will end with a summary of novel findings in RNA capping and the questions these findings pose.

Regulation of mRNA capping in the cell cycle

“…18 The mRNA cap binds to factors involved in transcription, mRNA processing and translation, and also protects the transcript from exonucleases. 4 However, the precise role of the mRNA cap on these different gene expression processes on a genome-wide level is only beginning to be documented in mammalian cells. Mutation of RNMT Thr-77 to alanine (T77A), which blocks phosphorylation did, not have a detectable effect on transcript level, despite significant depth of RNA sequencing analysis.…”

“…More recently formation and degradation of the mRNA cap has been observed to be regulated by cellular signaling pathways in mammalian cells. 4,5 The mRNA cap…”

“…Transcripts are synthesized with a 5 0 triphosphate on the first transcribed nucleotide to which the mRNA cap is added by the action of a series of enzymes. 1,4 In mammals the basic mRNA cap structure, cap 0, is formed by the sequential action of CE/RNGTT and RNMT-RAM, 2 enzymes recruited to phosphorylated RNA pol II at the initiation of transcription. CE/RNGTT has triphosphatase and guanylyltransferase activities which cleave the transcript terminal phosphate and catalyze addition of guanosine monophosphate, to form the cap structure, G(5 0 )ppp(5 0 )N (N is the first transcribed nucleotide).…”

“…7,8 O-2 methylation has roles in translation initiation and identifying transcripts as "self" in innate immunity. 4 …”

The RNA binding protein Mip6, a novel cellular partner of Mex67 export factor with implications in mRNA export

“…mRNA capping is critical, not only because it protects the pre-mRNA from 5´-3´exonuclease cleavage, but also for the recruitment of the splicing machinery through the nuclear CBC, polyadenylation, and ultimately nuclear export (Ramanathan, Robb, & Chan, 2016). …”