Abstract
The mRNA cap is a structure added to RNA pol II transcripts in eukaryotes, which recruits factors involved in RNA processing, nuclear export and translation initiation. RNA guanine-7 methyltransferase (RNMT)–RNA-activating miniprotein (RAM), the mRNA cap methyltransferase complex, completes the basic functional mRNA cap structure, cap 0, by methylating the cap guanosine. Here, we report that RNMT–RAM co-ordinates mRNA processing with ribosome production. Suppression of RNMT–RAM reduces synthesis of the 45S ribosomal RNA (rRNA) precursor. RNMT–RAM is required for c-Myc expression, a major regulator of RNA pol I, which synthesises 45S rRNA. Constitutive expression of c-Myc restores rRNA synthesis when RNMT–RAM is suppressed, indicating that RNMT–RAM controls rRNA production predominantly by controlling c-Myc expression. We report that RNMT–RAM is recruited to the ribosomal DNA locus, which may contribute to rRNA synthesis in certain contexts.
Highlights
In eukaryotes, gene expression is dependent on the mRNA cap being added to RNA pol II transcripts [1,2,3]
We report that RNA guanine-7 methyltransferase (RNMT)–RNA-activating miniprotein (RAM) is recruited to the ribosomal DNA locus, which may contribute to ribosomal RNA (rRNA) synthesis in certain contexts
To investigate the relationship between the mRNA cap methyltransferase, RNMT–RAM, and rRNA production, HeLa cells were transfected with two independent RAM siRNAs, an RNMT siRNA or a non-targeting control siRNA
Summary
Gene expression is dependent on the mRNA cap being added to RNA pol II transcripts [1,2,3]. The cap structure protects transcripts from nucleases and recruits factors that mediate RNA processing, export and translation initiation [4,5]. An N-7 RNA methyltransferase catalyses guanosine cap methylation to create the cap 0 structure, m7G(50)ppp(50)N. The cap can be further methylated on the first transcribed nucleotides, the cap 0 structure is sufficient to recruit cap-binding factors, including CBC (cap-binding complex) and eIF4E (eukaryotic initiation factor 4E), which promote splicing, nuclear export and translation initiation [4,5]. The methyltransferase, RNMT (RNA guanine-7 methyltransferase), catalyses mRNA cap methylation. RAM contains an RNA-binding domain that is required for efficient recruitment of transcripts to RNMT [9]. We demonstrate that RNMT–RAM controls ribosomal RNA (rRNA) production and present the mechanism involved
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