Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila

被引:47
作者
Burow, Dana A. [1 ,3 ]
Martin, Sophie [2 ]
Quail, Jade F. [1 ]
Alhusaini, Najwa [2 ]
Coller, Jeff [2 ]
Cleary, Michael D. [1 ]
机构
[1] Univ Calif Merced, Mol & Cell Biol Unit, Quantitat & Syst Biol Program, Merced, CA 95343 USA
[2] Case Western Reserve Univ, Ctr RNA Sci & Therapeut, Cleveland, OH 44106 USA
[3] Univ Calif San Diego, Dept Obstet Gynecol & Reprod Sci, Sch Med, La Jolla, CA 92093 USA
关键词
BINDING PROTEINS; GENE-EXPRESSION; TRANSLATION; STABILITY; USAGE; MELANOGASTER;
D O I
10.1016/j.celrep.2018.07.039
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tissue-specific mRNA stability is important for cell fate and physiology, but the mechanisms involved are not fully understood. We found that zygotic mRNA stability in Drosophila correlates with codon content: optimal codons are enriched in stable transcripts associated with metabolic functions like translation, while non-optimal codons are enriched in unstable transcripts, including those associated with neural development. Bioinformatic analyses and reporter assays revealed that similar codons stabilize or destabilize mRNAs in the nervous system and other tissues, but the link between codon content and stability is attenuated in the nervous system. We confirmed that optimal codons are decoded by abundant tRNAs while non-optimal codons are decoded by less abundant tRNAs in embryos and in the nervous system. We conclude that codon optimality is a general determinant of zygotic mRNA stability, and attenuation of codon optimality allows trans-acting factors to exert greater influence over mRNA decay in the nervous system.
引用
收藏
页码:1704 / 1712
页数:9
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