{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LSG1 is a highly conserved, circularly permuted GTPase that plays a critical role in the final cytoplasmic maturation of the large (60S) ribosomal subunit. In organisms ranging from yeast and plants to humans, LSG1 facilitates a key remodeling event by promoting the release of the nuclear export adapter Nmd3 and enabling the proper incorporation of late-assembling ribosomal proteins (e.g. uL16), thereby coupling nuclear export with the acquisition of translational competence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Biochemical and structural studies have shown that LSG1 preferentially binds GTP and, upon interaction with pre‐60S particles loaded with Nmd3, undergoes conformational changes that promote the dislodgement of Nmd3. Cryo‐electron microscopy analyses have further revealed that LSG1 acts in concert with other maturation factors, such as Tif6, to establish quality control checkpoints during ribosome assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its fundamental role in ribosome biogenesis, perturbation of LSG1 function has been linked to broader cellular consequences. For instance, inhibition of LSG1 triggers a robust cellular senescence response accompanied by endoplasmic reticulum stress and upregulation of the cholesterol biosynthesis pathway, suggesting that disturbances in 60S subunit maturation can have wide‐ranging effects on cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Evolutionary and functional studies in plants and model organisms further underscore the essential nature of this GTPase. In Arabidopsis thaliana, specific orthologues of LSG1 are required for normal ribosome biogenesis and plant development, while in Drosophila the protein NS3—which is functionally analogous to LSG1—is necessary for proper neuroblast proliferation and cell polarity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LSG1 acts as a pivotal regulator of 60S ribosomal subunit maturation by ensuring the proper release and recycling of ribosome biogenesis factors. Through its GTPase activity and interactions with key components of the ribosome assembly machinery, LSG1 not only safeguards the fidelity of protein synthesis but also influences cell growth, viability, and stress responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emmanuel G Reynaud, Miguel A Andrade, Fabien Bonneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1741-7007-3-21"}], "href": "https://doi.org/10.1186/1741-7007-3-21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16209721"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16209721"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "George Kallstrom, John Hedges, Arlen Johnson "}, {"type": "b", "children": [{"type": "t", "text": "The putative GTPases Nog1p and Lsg1p are required for 60S ribosomal subunit biogenesis and are localized to the nucleus and cytoplasm, respectively."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.12.4344-4355.2003"}], "href": "https://doi.org/10.1128/MCB.23.12.4344-4355.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12773575"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12773575"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "John Hedges, Matthew West, Arlen W Johnson "}, {"type": "b", "children": [{"type": "t", "text": "Release of the export adapter, Nmd3p, from the 60S ribosomal subunit requires Rpl10p and the cytoplasmic GTPase Lsg1p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600547"}], "href": "https://doi.org/10.1038/sj.emboj.7600547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15660131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15660131"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Matthew West, John B Hedges, Anthony Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defining the order in which Nmd3p and Rpl10p load onto nascent 60S ribosomal subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.9.3802-3813.2005"}], "href": "https://doi.org/10.1128/MCB.25.9.3802-3813.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15831484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15831484"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Andrey G Malyutin, Sharmishtha Musalgaonkar, Stephanie Patchett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nmd3 is a structural mimic of eIF5A, and activates the cpGTPase Lsg1 during 60S ribosome biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201696012"}], "href": "https://doi.org/10.15252/embj.201696012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28179369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28179369"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Juliana Jaramillo-Ramírez, Nancy Marcial-Bazaldua, Nuria Sánchez-Puig "}, {"type": "b", "children": [{"type": "t", "text": "Characterisation of the interaction of guanine nucleotides with ribosomal GTPase Lsg1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Proteins Proteom (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbapap.2020.140538"}], "href": "https://doi.org/10.1016/j.bbapap.2020.140538"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32916301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32916301"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Asimina Pantazi, Andrea Quintanilla, Priya Hari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.12981"}], "href": "https://doi.org/10.1111/acel.12981"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31148378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31148378"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Benjamin L Weis, Sandra Missbach, Julian Marzi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The 60S associated ribosome biogenesis factor LSG1-2 is required for 40S maturation in Arabidopsis thaliana."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Plant J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tpj.12703"}], "href": "https://doi.org/10.1111/tpj.12703"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25319368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25319368"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Tom A Hartl, Julie Ni, Jian Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of ribosome biogenesis by nucleostemin 3 promotes local and systemic growth in Drosophila."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genetics (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1534/genetics.112.149104"}], "href": "https://doi.org/10.1534/genetics.112.149104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23436180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23436180"}]}]}]}