{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CUTA is emerging as a multifunctional protein whose diverse roles span RNA metabolism, metal ion homeostasis, and neural as well as cellular trafficking processes across different organisms. In mammalian systems, studies have revealed that the copper‐related protein CUTA (often designated mCutA) interacts with the β‐site APP cleaving enzyme 1 (BACE1) and modulates the processing of amyloid precursor protein (APP) to attenuate β‐amyloid generation, thereby potentially influencing Alzheimer’s disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, mCutA appears to play a critical role in neural function by facilitating the proper localization of acetylcholinesterase at the cell surface, an activity that is vital for efficient cholinergic transmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its function in neural regulation, CUTA has been identified as a terminal nucleotidyltransferase that adds non‐templated nucleotides to the 3′ ends of RNA transcripts. This catalytic activity is central to the generation of specific 3′ “CUCU tags” on mRNAs that prime transcripts for decapping and degradation, thus contributing to post‐transcriptional gene regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In microbial and plant systems, CUTA homologs have been implicated in heavy metal tolerance. In bacteria, the gene product of cutA is required for copper tolerance and also affects resistance to other divalent cations, with studies demonstrating that CutA forms trimeric assemblies that bind Cu(II) ions and undergo reversible metal‐induced aggregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In Arabidopsis thaliana, the CUTA precursor localizes to chloroplast membranes where it binds copper with an affinity comparable to that of mammalian prion proteins, suggesting a conserved role in copper homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Complementing these functions, additional studies have hinted at further layers of complexity in CUTA biology. For instance, a mitochondrial isoform has been identified in human cells where CUTA forms trimers, raising the prospect of a role in intracellular signalling or energy metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, genetic studies have associated missense variants in the CUTA gene with an increased risk of idiopathic achalasia, while proteomic analyses have detected CUTA as a differentially abundant whey protein in cross‐bred sheep, suggesting potential contributions to organ function and lactation biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the pleiotropic roles of CUTA in regulating RNA stability, metal ion homeostasis, protein trafficking, and neural function – a spectrum of activities that renders it a key player in both normal physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ping Hou, Guiying Liu, Yingjun Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of copper and the copper-related protein CUTA in mediating APP processing and Aβ generation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2014.12.005"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2014.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25557959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25557959"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yingjun Zhao, Yunshu Wang, Jin Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CutA divalent cation tolerance homolog (Escherichia coli) (CUTA) regulates β-cleavage of β-amyloid precursor protein (APP) through interacting with β-site APP cleaving protein 1 (BACE1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.330209"}], "href": "https://doi.org/10.1074/jbc.M111.330209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22351782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22351782"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "A L Perrier, X Cousin, N Boschetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two distinct proteins are associated with tetrameric acetylcholinesterase on the cell surface."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M004289200"}], "href": "https://doi.org/10.1074/jbc.M004289200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10954708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10954708"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Amir Mossanen-Parsi, Daniele Parisi, Natasha Browne-Marke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Histone mRNA is subject to 3' uridylation and re-adenylation in Aspergillus nidulans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Microbiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/mmi.14613"}], "href": "https://doi.org/10.1111/mmi.14613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33047379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33047379"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Deepshikha Malik, Kamil Kobyłecki, Paweł Krawczyk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure and mechanism of CutA, RNA nucleotidyl transferase with an unusual preference for cytosine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkaa647"}], "href": "https://doi.org/10.1093/nar/gkaa647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32785623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32785623"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Igor Y Morozov, Meriel G Jones, Dave G Spiller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct roles for Caf1, Ccr4, Edc3 and CutA in the co-ordination of transcript deadenylation, decapping and P-body formation in Aspergillus nidulans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Microbiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2958.2010.07118.x"}], "href": "https://doi.org/10.1111/j.1365-2958.2010.07118.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20233300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20233300"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "S T Fong, J Camakaris, B T Lee "}, {"type": "b", "children": [{"type": "t", "text": "Molecular genetics of a chromosomal locus involved in copper tolerance in Escherichia coli K-12."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Microbiol (1995)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2958.1995.tb02286.x"}], "href": "https://doi.org/10.1111/j.1365-2958.1995.tb02286.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "7623666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/7623666"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yoshikazu Tanaka, Kouhei Tsumoto, Takeshi Nakanishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural implications for heavy metal-induced reversible assembly and aggregation of a protein: the case of Pyrococcus horikoshii CutA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(03)01402-9"}], "href": "https://doi.org/10.1016/s0014-5793(03"}, {"type": "t", "text": "01402-9) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14706845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14706845"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jason L Burkhead, Salah E Abdel-Ghany, Jonathan M Morrill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Arabidopsis thaliana CUTA gene encodes an evolutionarily conserved copper binding chloroplast protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Plant J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1365-313x.2003.01769.x"}], "href": "https://doi.org/10.1046/j.1365-313x.2003.01769.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12795705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12795705"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jingchun Yang, Huirong Yang, Lichong Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the human CUTA isoform2 present in the stably transfected HeLa cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-007-9152-9"}], "href": "https://doi.org/10.1007/s11033-007-9152-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17924204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17924204"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Quanlin Li, Weifeng Chen, Cheng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing reveals common and rare variants in immunologic and neurological genes implicated in achalasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2021.06.004"}], "href": "https://doi.org/10.1016/j.ajhg.2021.06.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34197731"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34197731"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xiaohu Su, Zhong Zheng, Liguo Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic profiling of ovine milk after grading up."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dairy Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0022029921000455"}], "href": "https://doi.org/10.1017/S0022029921000455"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33985604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33985604"}]}]}]}