ArticleRNA (New York, N.Y.)2015
An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis.
Article in RNA (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 26 citations in OpenAlex.
- Tissue-specific role of dTrmO in threonine decoding during Drosophila melanogaster development.Biological research · 2026Article
- Structures of KEOPS bound to tRNA reveal functional roles of the kinase Bud32.Nature communications · 2024Article
- O-Sialoglycoprotein Endopeptidase Deficiency Impairs Proteostasis and Induces Autophagy in Human Embryonic Stem Cells.International journal of molecular sciences · 2024Article
- tRNA Modifications and Dysregulation: Implications for Brain Diseases.Brain sciences · 2024Review
- Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A.Nucleic acids research · 2024Article
- RNA modifications in insects.Frontiers in insect science · 2024Review
- The life and times of a tRNA.RNA (New York, N.Y.) · 2023Review
- A paralog of Pcc1 is the fifth core subunit of the KEOPS tRNA-modifying complex in Archaea.Nature communications · 2023Article
- Conservation and Diversification of tRNA tInternational journal of molecular sciences · 2022Review
- Nuclear Functions of KaeA, a Subunit of the KEOPS Complex inInternational journal of molecular sciences · 2022Article
- Abundances of transfer RNA modifications and transcriptional levels of tRNA-modifying enzymes are sex-associated in mosquitoes.Insect biochemistry and molecular biology · 2022Article
- p53 Related Protein Kinase is Required for Arp2/3-Dependent Actin Dynamics of Hemocytes inFrontiers in cell and developmental biology · 2022Article
- The structural and functional workings of KEOPS.Nucleic acids research · 2021Review
- Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development.International journal of molecular sciences · 2020Article
- The tRNA biology · 2018Article
- tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy.European journal of human genetics : EJHG · 2017Article
- Modulation of the Proteostasis Machinery to Overcome Stress Caused by Diminished Levels of t6A-Modified tRNAs in Drosophila.Biomolecules · 2017Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
N(6)-threonylcarbamoyl-adenosine (t6A) is one of the few RNA modifications that is universally present in life. This modification occurs at high frequency at position 37 of most tRNAs that decode ANN codons, and stabilizes cognate anticodon-codon interactions. Nearly all genetic studies of the t6A pathway have focused on single-celled organisms. In this study, we report the isolation of an extensive allelic series in the Drosophila ortholog of the core t6A biosynthesis factor Kae1. kae1 hemizygous larvae exhibit decreases in t6A that correlate with allele strength; however, we still detect substantial t6A-modified tRNAs even during the extended larval phase of null alleles. Nevertheless, complementation of Drosophila Kae1 and other t6A factors in corresponding yeast null mutants demonstrates that these metazoan genes execute t6A synthesis. Turning to the biological consequences of t6A loss, we characterize prominent kae1 melanotic masses and show that they are associated with lymph gland overgrowth and ectopic generation of lamellocytes. On the other hand, kae1 mutants exhibit other phenotypes that reflect insufficient tissue growth. Interestingly, whole-tissue and clonal analyses show that strongly mitotic tissues such as imaginal discs are exquisitely sensitive to loss of kae1, whereas nonproliferating tissues are less affected. Indeed, despite overt requirements of t6A for growth of many tissues, certain strong kae1 alleles achieve and sustain enlarged body size during their extended larval phase. Our studies highlight tissue-specific requirements of the t6A pathway in a metazoan context and provide insights into the diverse biological roles of this fundamental RNA modification during animal development and disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.