{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent evidence has revealed that the LINC00961 locus encodes a conserved micropeptide, SPAAR (small regulatory polypeptide of amino acid response), which plays a critical role in controlling mTORC1 signaling. SPAAR localizes to late endosome/lysosome compartments, where it interacts with the lysosomal v-ATPase to selectively inhibit mTORC1 activation in response to amino acid stimulation. This mechanism is particularly important during skeletal muscle regeneration, as acute muscle injury is accompanied by downregulation of the SPAR-encoding lncRNA, thereby permitting efficient mTORC1 activation and facilitating tissue repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in muscle tissue, the LINC00961/SPAAR locus contributes to the regulation of endothelial cell function. Investigations into endothelial cell differentiation have demonstrated that both the lncRNA and its encoded SPAAR peptide are key regulators of angiogenesis, suggesting that the locus orchestrates a counter-regulatory network required for proper endothelial cell behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, the significance of the LINC00961/SPAAR locus extends to cardiovascular biology. Studies utilizing CRISPR/Cas9 knockout mouse models have revealed that loss of this locus is associated with sex-specific delays in post-natal growth and development, with concomitant alterations in basal cardiac function. SPAAR expression, particularly in cardiac endothelial cells and fibroblasts, shows a robust hypoxic response, and its absence leads to reduced left ventricular volumes and an increased risk area following myocardial infarction. These findings underscore a crucial role for the locus in modulating cardiovascular development, function, and responses to ischemic injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akinobu Matsumoto, Alessandra Pasut, Masaki Matsumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21034"}], "href": "https://doi.org/10.1038/nature21034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28024296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28024296"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Helen L Spencer, Rachel Sanders, Mounia Boulberdaa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvaa008"}], "href": "https://doi.org/10.1093/cvr/cvaa008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31990292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31990292"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ana-Mishel Spiroski, Rachel Sanders, Marco Meloni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22020969"}], "href": "https://doi.org/10.3390/ijms22020969"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33478078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33478078"}]}]}]}