{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that LARP7 plays a pivotal role in modulating cellular senescence and vascular aging. In response to DNA damage, activation of the ATM kinase triggers the extracellular shuttling and downregulation of LARP7, which in turn diminishes SIRT1 deacetylase activity and promotes the acetylation and enhanced transcriptional activity of key regulators such as p53 and NF‐κB. These molecular changes accelerate the accumulation of senescent cells and contribute to atherogenesis; indeed, overexpression of LARP7 has been shown to restore SIRT1 activity, reduce senescence signals, and ultimately decrease the extent of atherosclerotic lesions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Disruptions in LARP7 function also impact post‐transcriptional RNA processing crucial for male fertility. LARP7 acts as an essential cofactor for the 2′‑O‑methylation of U6 small nuclear RNA by promoting its loading onto box C/D snoRNP complexes; this modification is vital for maintaining splicing fidelity. Loss of LARP7 in mouse male germ cells results in defective U6 methylation, widespread pre‑mRNA splicing alterations, and ultimately culminates in spermatogenic failure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "Beyond its roles in aging and RNA processing, LARP7 is critical for proper embryonic growth and differentiation. Loss‐of‑function mutations in LARP7 have been implicated in primordial dwarfism through destabilization of Lin28 mRNA, thereby priming embryonic stem cells for premature differentiation. Moreover, emerging studies using mouse models of psoriasis suggest that LARP7 may also regulate inflammatory responses, hinting at a broader influence in tissue homeostasis and disease. Additional insights into these diverse functions are illustrated in recent reports."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pengyi Yan, Zixuan Li, Junhao Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.110038"}], "href": "https://doi.org/10.1016/j.celrep.2021.110038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34818543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34818543"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ping Yang, Shuo Wu, Yige Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 overexpression alleviates aortic senescence and atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.18388"}], "href": "https://doi.org/10.1111/jcmm.18388"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38818612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38818612"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xin Wang, Zhi-Tong Li, Yue Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARP7-Mediated U6 snRNA Modification Ensures Splicing Fidelity and Spermatogenesis in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2020.01.002"}], "href": "https://doi.org/10.1016/j.molcel.2020.01.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32017896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32017896"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qian Dai, Guangxin Luan, Li Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Primordial dwarfism gene maintains Lin28 expression to safeguard embryonic stem cells from premature differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2014.03.053"}], "href": "https://doi.org/10.1016/j.celrep.2014.03.053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24768001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24768001"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xiaodong Liang, Shuo Wu, Zilong Geng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 Suppresses Endothelial-to-Mesenchymal Transition by Coupling With TRIM28."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.121.319590"}], "href": "https://doi.org/10.1161/CIRCRESAHA.121.319590"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34503347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34503347"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Na Li, Yulei Liu "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 alleviates psoriasis symptoms in mice by regulating the SIRT1/NF-κB signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Allergol Immunopathol (Madr) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15586/aei.v51i1.765"}], "href": "https://doi.org/10.15586/aei.v51i1.765"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36617833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36617833"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Na Li, Yulei Liu "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 upregulates SIRT1 deacetylase activity and inhibits Th1/Th17 cytokine response in psoriatic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Allergol Immunopathol (Madr) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15586/aei.v51i6.959"}], "href": "https://doi.org/10.15586/aei.v51i6.959"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37937491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37937491"}]}]}]}