{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Lsm11 is a specialized Sm‐like protein that serves as an essential core component of the U7 small nuclear ribonucleoprotein (snRNP) complex required for the 3′‐end processing of replication‐dependent histone pre-mRNAs. In contrast to the canonical Sm core found in spliceosomal snRNPs, Lsm11—together with Lsm10—forms a unique U7-specific ring that recognizes the noncanonical Sm-binding site of U7 snRNA, driving the proper assembly of the processing machinery on histone transcripts."}, {"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 Lsm11 exhibits a bipartite structure with a long N-terminal region and a C-terminal domain composed of two Sm motifs separated by an extended spacer. The N-terminal region is implicated in recruiting critical processing factors—such as the zinc finger protein FLASH—thereby facilitating the engagement of cleavage/polyadenylation factors (e.g., CPSF73) to form the active histone cleavage complex, while the C-terminal domain is sufficient for selective assembly with U7 snRNA."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Through its interaction with FLASH, Lsm11 is pivotal in recruiting and positioning the endonuclease CPSF73 and associated polyadenylation factors to mediate the precise endonucleolytic cleavage of histone pre-mRNAs—a step essential for proper histone gene expression during the cell cycle."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, mutations and dysregulation of LSM11 have been linked to impaired U7 snRNP assembly and subsequent misprocessing of histone transcripts, which can lead to altered chromatin organization, genomic instability, and pathological conditions including autoinflammatory disorders such as Aicardi–Goutières syndrome and defects seen in spinal muscular atrophy. Aberrant LSM11 function is also emerging as a contributing factor in cancer cell viability and proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, Lsm11 is crucial for the spatial organization of histone locus bodies, ensuring the coordinated coupling of histone transcription with 3′-end processing. This integration is key to maintaining cell cycle progression and genomic integrity, underscoring the dual functionality of Lsm11 in both snRNP assembly and in establishing the competence of histone mRNA processing complexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ramesh S Pillai, Matthias Grimmler, Gunter Meister, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A complex containing the CPSF73 endonuclease and other polyadenylation factors associates with U7 snRNP and is recruited to histone pre-mRNA for 3'-end processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00653-12"}], "href": "https://doi.org/10.1128/MCB.00653-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23071092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23071092"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Katarzyna Bucholc, Wei Shen Aik, Xiao-Cui Yang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "FLASH is required for the endonucleolytic cleavage of histone pre-mRNAs but is dispensable for the 5' exonucleolytic degradation of the downstream cleavage product."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00979-10"}], "href": "https://doi.org/10.1128/MCB.00979-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245389"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wei Shen Aik, Min-Han Lin, Dazhi Tan, et al. 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