{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe addition of a 7‐methylguanosine cap to the 5′ end of RNA polymerase II transcripts is a critical prerequisite for efficient gene expression in eukaryotes. In mammals, this modification is catalyzed by the RNA guanine-7 methyltransferase (RNMT), which forms a heterodimer with the RNMT-activating mini‐protein (RAM). RAM, possessing an N-terminal activating domain and a C-terminal RNA-binding domain, not only stabilizes and fully activates RNMT but also significantly enhances its affinity for RNA substrates, ensuring effective cap methylation, proper mRNA expression and translation, and overall cell viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMolecular dynamics studies have elucidated the mechanism by which RAM allosterically regulates RNMT, selecting active site conformations that are optimal for binding both the methyl donor S-adenosyl methionine (AdoMet) and the mRNA cap substrate. These investigations suggest that cap binding itself further promotes AdoMet engagement, supporting a cooperative binding model that underpins robust catalytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in mRNA cap formation, the RNMT–RAM complex has been shown to intersect with ribosome biogenesis. By controlling the expression of c-Myc—a pivotal regulator of RNA polymerase I transcription—the complex indirectly governs the synthesis of the 45S ribosomal RNA precursor. Additionally, recruitment of RNMT–RAM to the ribosomal DNA locus underscores a potential direct contribution to rRNA production under specific cellular contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Gonatopoulos-Pournatzis, Sianadh Dunn, Rebecca Bounds, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RAM/Fam103a1 is required for mRNA cap methylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2011.08.041"}], "href": "https://doi.org/10.1016/j.molcel.2011.08.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22099306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22099306"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thomas Gonatopoulos-Pournatzis, Victoria H Cowling "}, {"type": "b", "children": [{"type": "t", "text": "RAM function is dependent on Kapβ2-mediated nuclear entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20131359"}], "href": "https://doi.org/10.1042/BJ20131359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24200467"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24200467"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Juan A Bueren-Calabuig, Marcus G Bage, Victoria H Cowling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: insights from accelerated molecular dynamics simulations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkz613"}], "href": "https://doi.org/10.1093/nar/gkz613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31329932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31329932"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sianadh Dunn, Olivia Lombardi, Victoria H Cowling "}, {"type": "b", "children": [{"type": "t", "text": "c-Myc co-ordinates mRNA cap methylation and ribosomal RNA production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20160930"}], "href": "https://doi.org/10.1042/BCJ20160930"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27934633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27934633"}]}]}]}