气候变化领域集成服务门户(CCPortal): Tissue-specific dynamic codon redefinition in Drosophila

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DOI	10.1073/pnas.2012793118
	Tissue-specific dynamic codon redefinition in Drosophila
	Hudson A.M.; Szabo N.L.; Loughran G.; Wills N.M.; Atkins J.F.; Cooley L.
发表日期	2021
ISSN	00278424
卷号	118 期号:5
英文摘要	Translational stop codon readthrough occurs in organisms ranging from viruses to mammals and is especially prevalent in decoding Drosophila and viral mRNAs. Recoding of UGA, UAG, or UAA to specify an amino acid allows a proportion of the protein encoded by a single gene to be C-terminally extended. The extended product from Drosophila kelch mRNA is 160 kDa, whereas unextended Kelch protein, a subunit of a Cullin3-RING ubiquitin ligase, is 76 kDa. Previously we reported tissue-specific regulation of readthrough of the first kelch stop codon. Here, we characterize major efficiency differences in a variety of cell types. Immunoblotting revealed low levels of readthrough in malpighian tubules, ovary, and testis but abundant readthrough product in lysates of larval and adult central nervous system (CNS) tissue. Reporters of readthrough demonstrated greater than 30% readthrough in adult brains, and imaging in larval and adult brains showed that readthrough occurred in neurons but not glia. The extent of readthrough stimulatory sequences flanking the readthrough stop codon was assessed in transgenic Drosophila and in human tissue culture cells where inefficient readthrough occurs. A 99-nucleotide sequence with potential to form an mRNA stem-loop 3′ of the readthrough stop codon stimulated readthrough efficiency. However, even with just six nucleotides of kelch mRNA sequence 3′ of the stop codon, readthrough efficiency only dropped to 6% in adult neurons. Finally, we show that high-efficiency readthrough in the Drosophila CNS is common; for many neuronal proteins, C-terminal extended forms of individual proteins are likely relatively abundant. © 2020 Proceedings of the National Academy of Sciences of the United States of America. All rights reserved.
英文关键词	Central nervous system (CNS); Drosophila; Kelch; Recoding; Stop codon readthrough
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180832
作者单位	Department of Genetics, Yale School of Medicine, New Haven, CT 06520, United States; Schools of Biochemistry and Microbiology, University College Cork, Cork, T12 XF62, Ireland; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, United States; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, United States; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, United States
推荐引用方式 GB/T 7714	Hudson A.M.,Szabo N.L.,Loughran G.,et al. Tissue-specific dynamic codon redefinition in Drosophila[J],2021,118(5).
APA	Hudson A.M.,Szabo N.L.,Loughran G.,Wills N.M.,Atkins J.F.,&Cooley L..(2021).Tissue-specific dynamic codon redefinition in Drosophila.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA	Hudson A.M.,et al."Tissue-specific dynamic codon redefinition in Drosophila".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).