The Mammalian Cap-Specific m6Am RNA Methyltransferase PCIF1 Regulates Transcript Levels in Mouse Tissues

New publication by the Pillai group on "The Mammalian Cap-Specific m6Am RNA Methyltransferase PCIF1 Regulates Transcript Levels in Mouse Tissues" published in Cell Reports.

Highlights

  • Mouse mutants of the m6Am methylase Pcif1 display reduced body weight
  • Transcripts with a TSS adenosine are destabilized in the Pcif1 mutant mice
  • Catalytically dead Drosophila Pcif1 binds Ser5-phospho CTD
  • Trypanosoma Pcif1 is an m6Am methylase that creates the cap4 structure

Summary

The 5' end of eukaryotic mRNAs is protected by the m7G-cap structure. The transcription start site nucleotide is ribose methylated (Nm) in many eukaryotes, whereas an adenosine at this position is further methylated at the N6 position (m6A) by the mammalian Phosphorylated C-terminal domain (CTD)-interacting Factor 1 (PCIF1) to generate m6Am. Here, we show that although the loss of cap-specific m6Am in mice does not affect viability or fertility, the Pcif1 mutants display reduced body weight. Transcriptome analyses of mutant mouse tissues support a role for the cap-specific m6Am modification in stabilizing transcripts. In contrast, the Drosophila Pcif1 is catalytically dead, but like its mammalian counterpart, it retains the ability to associate with the Ser5-phosphorylated CTD of RNA polymerase II (RNA Pol II). Finally, we show that the Trypanosoma Pcif1 is an m6Am methylase that contributes to the N6,N6,2'-O-trimethyladenosine (m62Am) in the hypermethylated cap4 structure of trypanosomatids. Thus, PCIF1 has evolved to function in catalytic and non-catalytic roles.

Read the Publication in Cell Reports (Open Access)

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Graphical abstract, highlights, summary & title from Pandey et al. (2020) Cell Reports published under the CC BY-NC-ND 4.0 License.