{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Maf1 is a highly conserved global regulator that negatively controls RNA polymerase III transcription across eukaryotes. Early studies in yeast established Maf1 as a repressor of tRNA and 5S rRNA synthesis, acting by interfering with the assembly of essential transcription initiation complexes such as TFIIIB and directly associating with RNA polymerase III (a finding later corroborated by cryo‐EM structural studies showing Maf1 occluding key polymerase elements)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In mammalian cells, Maf1 retains its function as a transcriptional repressor of RNA polymerase III genes and extends its regulatory influence to modulation of RNA polymerases I and II, thereby impacting overall biosynthetic capacity and cellular transformation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Maf1 activity is tightly coupled to nutrient and stress signaling pathways. In both yeast and mammals, signaling via the target of rapamycin (TOR/mTOR) pathway modulates Maf1 through phosphorylation: under favorable conditions Maf1 is phosphorylated and largely cytoplasmic, whereas stress or mTOR inhibition induces its dephosphorylation and consequent nuclear accumulation, leading to robust repression of RNA polymerase III–driven transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Recent work has further highlighted the importance of post‐translational modifications, as SUMOylation of Maf1 at key lysine residues significantly contributes to its ability to repress transcription by affecting its interaction with RNA polymerase III."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, the structural integrity and interplay between Maf1’s conserved domains underpin its regulatory function, with studies in yeast demonstrating that disruption of these interactions impairs its dephosphorylation and ability to inhibit transcription."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its core role in transcriptional repression, Maf1 has emerged as a critical effector in controlling cell growth and transformation. In human cells, reduced Maf1 expression is linked to enhanced ribosomal and tRNA synthesis, contributing to oncogenic processes, while Maf1 itself can promote tumor suppressor activity through indirect pathways such as activating PTEN."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Notably, while diverse kinases (including PKA/Sch9 and CK2) phosphorylate Maf1, evidence indicates that regulation by these kinases does not further modify its ability to derepress transcription when cells shift from repressive to growth conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, Maf1 serves as a central node integrating nutritional and stress signals to modulate RNA polymerase III activity—and by extension, overall cellular biosynthetic capacity—through direct interactions and post‐translational modifications. Its conserved function from yeast to man underscores its importance in maintaining transcriptional homeostasis and influencing cell growth, with alterations in Maf1 activity being implicated in pathological conditions such as cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rajendra Upadhya, JaeHoon Lee, Ian M Willis "}, {"type": "b", "children": [{"type": "t", "text": "Maf1 is an essential mediator of diverse signals that repress RNA polymerase III transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00787-6"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00787-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12504022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12504022"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Matthias K Vorländer, Florence Baudin, Robyn D Moir, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1005188107"}], "href": "https://doi.org/10.1073/pnas.1005188107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20543138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20543138"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "K Pluta, O Lefebvre, N C Martin, et al. 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