{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LSm8 is a critical component of the nuclear LSm2–8 complex that plays multifaceted roles in RNA metabolism. As part of this complex, LSm8 mediates the selective binding and stabilization of U6 small nuclear RNA (snRNA), ensuring its proper 3′‐end recognition and incorporation into the spliceosome for efficient pre-mRNA splicing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In addition, LSm8 is instrumental in RNP assembly pathways beyond splicing; for example, it contributes to telomerase biogenesis by enabling binding of the LSm2–8 ring to telomerase RNA, thereby promoting the assembly of catalytically active telomerase complexes required for telomere maintenance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n LSm8 also exerts regulatory control over the subcellular distribution and activity of LSm complexes. Unlike its cytoplasmic paralogues that participate in mRNA decay foci, LSm8 is predominantly nuclear; its expression helps retain LSm2–7 proteins in the nucleus, with depletion of LSm8 leading to an increased number of cytoplasmic processing bodies (P‐bodies)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In this nuclear context, the LSm2–8 complex further contributes to mRNA surveillance by targeting select transcripts for decapping and degradation, thereby coupling RNA processing with turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, studies in evolutionarily divergent organisms such as trypanosomes reveal that LSm8 not only fulfills its canonical role in U6 snRNA stabilization and splicing but may also participate in mRNA decay, underscoring its conserved yet adaptable functions across species."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings highlight LSm8 as a pivotal regulator that integrates pre-mRNA splicing, RNP assembly, and RNA degradation, thereby maintaining RNA homeostasis in both normal and stress-responsive cellular contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "E Bouveret, G Rigaut, A Shevchenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Sm-like protein complex that participates in mRNA degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/19.7.1661"}], "href": "https://doi.org/10.1093/emboj/19.7.1661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10747033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10747033"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lijun Zhou, Jing Hang, Yulin Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structures of the Lsm complex bound to the 3' end sequence of U6 small nuclear RNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature12803"}], "href": "https://doi.org/10.1038/nature12803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24240276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24240276"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "B K Pannone, S D Kim, D A Noe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple functional interactions between components of the Lsm2-Lsm8 complex, U6 snRNA, and the yeast La protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genetics (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/genetics/158.1.187"}], "href": "https://doi.org/10.1093/genetics/158.1.187"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11333229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11333229"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Allen J Roth, Stewart Shuman, Beate Schwer "}, {"type": "b", "children": [{"type": "t", "text": "Defining essential elements and genetic interactions of the yeast Lsm2-8 ring and demonstration that essentiality of Lsm2-8 is bypassed via overexpression of U6 snRNA or the U6 snRNP subunit Prp24."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.066175.118"}], "href": "https://doi.org/10.1261/rna.066175.118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29615482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29615482"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Diego J Páez-Moscoso, Lili Pan, Rutendo F Sigauke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pof8 is a La-related protein and a constitutive component of telomerase in fission yeast."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-02284-8"}], "href": "https://doi.org/10.1038/s41467-017-02284-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29422664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29422664"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dierk Ingelfinger, Donna J Arndt-Jovin, Reinhard Lührmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12515382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12515382"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ivan Novotny, Katerina Podolská, Michaela Blazíková, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear LSm8 affects number of cytoplasmic processing bodies via controlling cellular distribution of Like-Sm proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E12-02-0085"}], "href": "https://doi.org/10.1091/mbc.E12-02-0085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22875987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22875987"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Joanna Kufel, Cecile Bousquet-Antonelli, Jean D Beggs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear pre-mRNA decapping and 5' degradation in yeast require the Lsm2-8p complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.21.9646-9657.2004"}], "href": "https://doi.org/10.1128/MCB.24.21.9646-9657.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15485930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15485930"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Anna Mattout, Dimos Gaidatzis, Jan Padeken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-020-0504-1"}], "href": "https://doi.org/10.1038/s41556-020-0504-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32251399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32251399"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Qing Liu, Xue-hai Liang, Shai Uliel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional characterization of lsm proteins in Trypanosoma brucei."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M400678200"}], "href": "https://doi.org/10.1074/jbc.M400678200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14990572"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14990572"}]}]}]}