Regulation of mRNA capping in the cell cycle

Abstract

The mRNA cap structure, which is added to nascent RNA pol II transcripts, recruits the protein complexes required for pre-mRNA transcript processing, mRNA export and translation initiation. The enzymes which catalyze mRNA cap synthesis are regulated by cellular signaling pathways which impact on their expression, localization and activity. Here we discuss the recent observation that the mRNA cap methyltransferase, RNMT, is phosphorylated on Thr-77 by CDK1-cyclin B1, which regulates its activity and the proteins with which it interacts. RNMT Thr-77 phosphorylation provides a burst of mRNA cap methyltransferase activity during early G1 phase at a time when transcription is reactivated following completion of the cell cycle. This co-ordination of transcription and mRNA capping makes an important contribution to gene expression in the cell; preventing RNMT Thr-77 phosphorylation inhibits cell proliferation. Here we discuss these findings and how mRNA cap synthesis may be regulated in other scenarios.

Keywords: Cell cycle; RNMT; gene expression; mRNA; mRNA cap; phosphorylation; transcription; translation.

Figure 1.

mRNA cap structure and mRNA capping enzymes. Structure of mRNA cap and action of mRNA capping enzymes.

Figure 2.

Post-translational modifications of RNMT. Human RNMT 1-120 is the N-terminal domain and RNMT 121-476 is the catalytic domain and interacts with RAM. Above depiction of RNMT are phosphorylation sites (P) obtained from PhosphositePlus (sites with only 1 mass spectrometry/high-throughput proteomics reference excluded). Below depiction of RNMT are phosphorylation, acetylation (Ac) and methylation (Me) sites identified from analysis in Aregger et al., 2016.