Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila
Summary: 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 funct...
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doaj-d329f5098bbd4e6a86dd22b54798e8e62020-11-24T21:21:03ZengElsevierCell Reports2211-12472018-08-0124717041712Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in DrosophilaDana A. Burow0Sophie Martin1Jade F. Quail2Najwa Alhusaini3Jeff Coller4Michael D. Cleary5Molecular and Cell Biology Unit, Quantitative and Systems Biology Program, University of California, Merced, Merced, CA 95343, USACenter for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USAMolecular and Cell Biology Unit, Quantitative and Systems Biology Program, University of California, Merced, Merced, CA 95343, USACenter for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USACenter for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USAMolecular and Cell Biology Unit, Quantitative and Systems Biology Program, University of California, Merced, Merced, CA 95343, USA; Corresponding authorSummary: 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. : Burow et al. report that codon optimality is a general determinant of zygotic mRNA stability in Drosophila embryos, but the link between codons and stability is weak in the nervous system. Bioinformatics, reporter transcript assays, and tRNA quantitation show that the attenuation of codon optimality establishes neural-specific mRNA decay. Keywords: codon optimality, mRNA stability, development, nervous system, tRNA, Drosophilahttp://www.sciencedirect.com/science/article/pii/S221112471831129X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dana A. Burow Sophie Martin Jade F. Quail Najwa Alhusaini Jeff Coller Michael D. Cleary |
spellingShingle |
Dana A. Burow Sophie Martin Jade F. Quail Najwa Alhusaini Jeff Coller Michael D. Cleary Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila Cell Reports |
author_facet |
Dana A. Burow Sophie Martin Jade F. Quail Najwa Alhusaini Jeff Coller Michael D. Cleary |
author_sort |
Dana A. Burow |
title |
Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila |
title_short |
Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila |
title_full |
Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila |
title_fullStr |
Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila |
title_full_unstemmed |
Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila |
title_sort |
attenuated codon optimality contributes to neural-specific mrna decay in drosophila |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-08-01 |
description |
Summary: 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. : Burow et al. report that codon optimality is a general determinant of zygotic mRNA stability in Drosophila embryos, but the link between codons and stability is weak in the nervous system. Bioinformatics, reporter transcript assays, and tRNA quantitation show that the attenuation of codon optimality establishes neural-specific mRNA decay. Keywords: codon optimality, mRNA stability, development, nervous system, tRNA, Drosophila |
url |
http://www.sciencedirect.com/science/article/pii/S221112471831129X |
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