{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough traditional chromatin regulators such as BRPF3 have been shown to form functional complexes essential for development and epigenetic regulation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", emerging research has uncovered a novel class of small proteins encoded by long noncoding RNAs. One notable example is SMIM26, a microprotein produced from the LINC00493 transcript, which has attracted attention for its distinct mitochondrial functions and roles in cellular regulation.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRibosome-profiling and proteomic analyses have confirmed that LINC00493 harbors a small open reading frame that is translated into a 95–amino acid product, SMIM26. Immunofluorescence studies further revealed that SMIM26 localizes specifically to mitochondria, and its interaction network includes several mitochondrial proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctionally, SMIM26 has been implicated in cancer biology, particularly in clear cell renal cell carcinoma (ccRCC). In ccRCC, SMIM26 is tendentiously downregulated and its reduced expression correlates with poor overall survival. Mechanistically, SMIM26 exerts anti-metastatic effects by interacting via its N-terminus with acylglycerol kinase (AGK) and the glutathione transport regulator SLC25A11, which enhances the mitochondrial localization of AGK. This interaction inhibits AGK-mediated AKT phosphorylation and supports mitochondrial glutathione import and respiratory efficiency. Intriguingly, complementary knockdown and overexpression experiments indicate that while the SMIM26 protein suppresses tumor cell growth and metastatic lung colonization, the parent LINC00493 transcript appears to affect cell viability in the opposite direction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kezhi Yan, Linya You, Cindy Degerny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Chromatin Regulator BRPF3 Preferentially Activates the HBO1 Acetyltransferase but Is Dispensable for Mouse Development and Survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M115.703041"}], "href": "https://doi.org/10.1074/jbc.M115.703041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26677226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26677226"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fouzia Yeasmin, Naoto Imamachi, Tanzina Tanu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and analysis of short open reading frames (sORFs) in the initially annotated noncoding RNA LINC00493 from human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvaa143"}], "href": "https://doi.org/10.1093/jb/mvaa143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33386847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33386847"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daria Konina, Peter Sparber, Iuliia Viakhireva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of LINC00493/SMIM26 Gene Suggests Its Dual Functioning at mRNA and Protein Level."}]}, {"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/ijms22168477"}], "href": "https://doi.org/10.3390/ijms22168477"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34445188"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34445188"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kun Meng, Shaohua Lu, Yu-Ying Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.202256282"}], "href": "https://doi.org/10.15252/embr.202256282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37009826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37009826"}]}]}]}