{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LARP7 is a multifunctional RNA‐binding protein that plays a central role in maintaining the integrity and function of the 7SK small nuclear ribonucleoprotein (snRNP) complex. By binding the conserved UUU–3′OH and other U‐rich elements located at the 3′ end of 7SK RNA"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", LARP7 stabilizes the RNA scaffold and is essential for assembling a functional 7SK snRNP. This complex sequesters the positive transcription elongation factor b (P-TEFb) in an inactive state, thereby regulating RNA polymerase II transcriptional elongation by controlling the balance between free and inactive P-TEFb pools."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its core role in 7SK snRNA stabilization, LARP7 acts as a negative regulator of transcription; its presence limits the release of P-TEFb and, consequently, RNA polymerase II pause release is restrained until proper activating signals are received."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, structural studies of the La module of LARP7 have revealed unique features in its dual-domain organization that underpin its specific recognition of 7SK RNA, emphasizing its versatility in mediating key protein–RNA interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond transcription elongation control, emerging evidence indicates that LARP7 is also involved in other RNA regulatory processes. For example, it functions as a bridging factor that connects the spliceosomal U6 snRNA with specific box C/D small nucleolar RNAs to promote 2′-O-methylation of U6. This modification is crucial for splicing fidelity and proper gene expression in development and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, deficiency or mutation of LARP7 disrupts 7SK snRNP integrity and leads to aberrant P-TEFb activation. Such dysregulation has been implicated in pathological conditions including impaired differentiation, cellular senescence, and tumorigenesis, as seen in gastric cancers and developmental disorders like Alazami syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LARP7 functions as a key safeguard of transcriptional homeostasis. By stabilizing the 7SK RNA and regulating P-TEFb availability, it modulates RNA polymerase II elongation, and through additional roles in RNA modification, it contributes to splicing accuracy and cellular growth control. These multifaceted activities underscore its importance in normal cellular physiology and its emerging role in the etiology of diverse human diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brian J Krueger, Célia Jeronimo, Bibhuti Bhusan Roy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkn061"}], "href": "https://doi.org/10.1093/nar/gkn061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18281698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18281698"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andreas Markert, Michael Grimm, Javier Martinez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The La-related protein LARP7 is a component of the 7SK ribonucleoprotein and affects transcription of cellular and viral polymerase II genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/embor.2008.72"}], "href": "https://doi.org/10.1038/embor.2008.72"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18483487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18483487"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Emiko Uchikawa, Kundhavai S Natchiar, Xiao Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural insight into the mechanism of stabilization of the 7SK small nuclear RNA by LARP7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkv173"}], "href": "https://doi.org/10.1093/nar/gkv173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25753663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25753663"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yulan Cheng, Zhe Jin, Rachana Agarwal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LARP7 is a potential tumor suppressor gene in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/labinvest.2012.59"}], "href": "https://doi.org/10.1038/labinvest.2012.59"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22488152"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22488152"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daniele Hasler, Rajyalakshmi Meduri, Maciej Bąk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Alazami Syndrome-Associated Protein LARP7 Guides U6 Small Nuclear RNA Modification and Contributes to Splicing Robustness."}]}, {"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.2020.01.001"}], "href": "https://doi.org/10.1016/j.molcel.2020.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32017898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32017898"}]}, {"type": "r", "ref": 6, "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": 7, "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": 8, "children": [{"type": "t", "text": "Samuel R Witus, Mikaela D Stewart, Rachel E Klevit "}, {"type": "b", "children": [{"type": "t", "text": "The BRCA1/BARD1 ubiquitin ligase and its substrates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20200864"}], "href": "https://doi.org/10.1042/BCJ20200864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34591954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34591954"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jiayu Zhang, Rongguo Yu, Xiaoyu Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1933743"}], "href": "https://doi.org/10.1080/21655979.2021.1933743"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34107850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34107850"}]}]}]}