{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided studies directly examine SNORD84, the collective insights from these diverse investigations into cardiomyopathy, muscle function, and neurodegeneration help define the broader regulatory networks in which small non‐coding RNAs—such as SNORD84—may participate. In general, small nucleolar RNAs are known to guide chemical modifications (for example, 2′‑O‑methylation) of ribosomal RNAs and other RNA species, thereby fine‑tuning ribosome biogenesis and protein synthesis. Given that many of these studies document how precise regulation of protein expression (including key players like muscle LIM protein [MLP]) dictates cellular responses during stress and injury, it is plausible that SNORD84 contributes to these processes by indirectly influencing the translational capacity and homeostasis in tissues under pathological stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn studies of heart muscle disease and cardiac remodeling, loss‑ or mutation‑driven deficiencies in proteins such as MLP result in maladaptive responses including dilated cardiomyopathy, impaired contractility, and disrupted Ca²⁺ handling. These findings underscore the importance of tight post‑transcriptional and post‑translational regulatory mechanisms in the heart. Although the mechanistic evaluations in these models focused on protein–protein interactions and signaling cascades (for example, MLP’s role at the sarcomeric Z‑disk and its influence on calcineurin–NFAT activation), such cellular processes might also be influenced by small nucleolar RNAs that regulate ribosomal function and thereby protein synthesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the myocardium, research in neuronal and sensory systems has revealed that orchestrated changes in gene expression are critical for regeneration and developmental homeostasis. For example, induced expression of MLP in retinal ganglion cells promotes axon regrowth, suggesting that modulation of the cytoskeleton and transcriptional programs is essential for nerve repair. Although these studies concentrate on protein regulators, they highlight a cellular context in which RNA‐directed modifications—potentially mediated by snoRNAs like SNORD84—may support the adaptive responses required for tissue regeneration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, investigations into skeletal muscle insulin sensitivity demonstrate that aberrant protein expression and signaling can lead to insulin resistance. The downregulation of proteins such as CSRP3 (which encodes MLP) in insulin‐resistant states further emphasizes the critical role of coordinated gene expression in metabolic homeostasis. While these works focused primarily on protein factors and signaling molecules, RNA modifications guided by snoRNAs—including SNORD84—may represent an additional regulatory layer ensuring proper translation and function during metabolic stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joerg Heineke, Hartmut Ruetten, Christian Willenbockel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0405488102"}], "href": "https://doi.org/10.1073/pnas.0405488102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15665106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15665106"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ilka Lorenzen-Schmidt, Bruno D Stuyvers, Henk E D J ter Keurs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Young MLP deficient mice show diastolic dysfunction before the onset of dilated cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2005.05.006"}], "href": "https://doi.org/10.1016/j.yjmcc.2005.05.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15978612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15978612"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peter N Costandi, Lawrence R Frank, Andrew D McCulloch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of diastolic properties in the transition to failure in a mouse model of the cardiac dilatation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00571.2006"}], "href": "https://doi.org/10.1152/ajpheart.00571.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16861693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16861693"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Christian Kuhn, Derk Frank, Franziska Dierck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cardiac remodeling is not modulated by overexpression of muscle LIM protein (MLP)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Basic Res Cardiol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00395-012-0262-8"}], "href": "https://doi.org/10.1007/s00395-012-0262-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22421737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22421737"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mehroz Ehsan, Matthew Kelly, Charlotte Hooper, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutant Muscle LIM Protein C58G causes cardiomyopathy through protein depletion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2018.07.248"}], "href": "https://doi.org/10.1016/j.yjmcc.2018.07.248"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30048712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30048712"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jiayang Li, Kenneth S Gresham, Ranganath Mamidi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sarcomere-based genetic enhancement of systolic cardiac function in a murine model of dilated cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cardiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijcard.2018.09.073"}], "href": "https://doi.org/10.1016/j.ijcard.2018.09.073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30279005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30279005"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ralph Knöll, Sawa Kostin, Stefanie Klede, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A common MLP (muscle LIM protein) variant is associated with cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.109.206243"}], "href": "https://doi.org/10.1161/CIRCRESAHA.109.206243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20044516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20044516"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ajmal Gardiwal, Gunnar Klein, Kirsten Kraemer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced delayed rectifier K+ current, altered electrophysiology, and increased ventricular vulnerability in MLP-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Card Fail (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cardfail.2007.04.015"}], "href": "https://doi.org/10.1016/j.cardfail.2007.04.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17923363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17923363"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chun-Li Zhang, Yuhua Zou, Ruth T Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1413606"}], "href": "https://doi.org/10.1101/gad.1413606"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16702404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16702404"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Mingyao Ying, Rener Xu, Xiaohui Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M511677200"}], "href": "https://doi.org/10.1074/jbc.M511677200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16407196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16407196"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Vasiliki Papalouka, Demetrios A Arvanitis, Elizabeth Vafiadaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00654-09"}], "href": "https://doi.org/10.1128/MCB.00654-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19752190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19752190"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Rong Hou, Nicholas E S Sibinga "}, {"type": "b", "children": [{"type": "t", "text": "Atrophin proteins interact with the Fat1 cadherin and regulate migration and orientation in vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M809333200"}], "href": "https://doi.org/10.1074/jbc.M809333200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19131340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19131340"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yiguo Shen, Gena Lee, Youngshik Choe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional architecture of atrophins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M610274200"}], "href": "https://doi.org/10.1074/jbc.M610274200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17150957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17150957"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Juehua Yu, Mingyao Ying, Yuan Zhuang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C-terminal deletion of the atrophin-1 protein results in growth retardation but not neurodegeneration in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.22063"}], "href": "https://doi.org/10.1002/dvdy.22063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19681162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19681162"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Evgeny Levin, Marco Leibinger, Philipp Gobrecht, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscle LIM Protein Is Expressed in the Injured Adult CNS and Promotes Axon Regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.12.026"}], "href": "https://doi.org/10.1016/j.celrep.2018.12.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30673598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30673598"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Angelina Hernandez-Carretero, Natalie Weber, Samuel A LaBarge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cysteine- and glycine-rich protein 3 regulates glucose homeostasis in skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.00435.2017"}], "href": "https://doi.org/10.1152/ajpendo.00435.2017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29634311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29634311"}]}]}]}