{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent genomic and functional analyses have revealed that MPP6 plays multifaceted roles in human health, directly impacting sleep physiology as well as RNA metabolism. A genome‐wide association study identified MPP6 as a novel gene linked to sleep quality, where its reduced expression in sleep center neurons of Drosophila led to shortened sleep duration, highlighting its functional relevance in sleep regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical investigations further established that MPP6 is integral to RNA decay processes by facilitating the recruitment of MTR4 to the exosome complex. In this context, MPP6 works redundantly with RRP6 to promote the decay of specific RNA substrates transcribed by RNA polymerase II; however, MTR4 binding via MPP6 appears to mediate the decay of a distinct subset of these substrates, underscoring its specialized role in exosome activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe involvement of MPP6 extends into oncological settings; despite its recognized roles within the membrane palmitoylated protein family in influencing cell adhesion and polarity, its specific function in hepatocellular carcinoma remains unexplored."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in colorectal cancer, an alternatively spliced circular RNA derived from MPP6, termed circMPP6, functions as a molecular scaffold. This circRNA facilitates the interaction between MEX3A—a RNA-binding protein implicated in cancer aggressiveness—and other processing body proteins, thereby modulating liquid-liquid phase separation dynamics and promoting the degradation of mRNAs such as PDE5A, which contributes to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Samar Khoury, Qiao-Ping Wang, Marc Parisien, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sleep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/sleep/zsaa211"}], "href": "https://doi.org/10.1093/sleep/zsaa211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33034629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33034629"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Naoko Fujiwara, Maki Shigemoto, Mizuki Hirayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkac559"}], "href": "https://doi.org/10.1093/nar/gkac559"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35902094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35902094"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qianqian Cheng, Wei Wang, Jing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "MPP6"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " expression correlates with an unfavorable prognosis, angiogenesis and immune evasion in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2023.1173848"}], "href": "https://doi.org/10.3389/fimmu.2023.1173848"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37207207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37207207"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ri-Xin Chen, Shui-Dan Xu, Min-Hua Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Signal Transduct Target Ther (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41392-024-01787-3"}], "href": "https://doi.org/10.1038/s41392-024-01787-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38565536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38565536"}]}]}]}