An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis

Simple item page
dc.contributor.authorLin, Ching-Jung
dc.contributor.authorSmibert, Peter
dc.contributor.authorZhao, Xiaoyu
dc.contributor.authorHu, Jennifer F.
dc.contributor.authorRamroop, Johnny
dc.contributor.authorKellner, Stefanie M.
dc.contributor.authorBenton, Matthew
dc.contributor.authorGovind, Shubha
dc.contributor.authorDedon, Peter C.
dc.contributor.authorSternglanz, Rolf
dc.contributor.authorLai, Eric C.
dc.date.accessioned2016-02-24T22:41:25Z
dc.date.issued2015
dc.date.updated2016-02-24T10:11:48Z
dc.description.abstractN6-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.
dc.identifier.issn1355-8382
dc.identifier.urihttp://hdl.handle.net/1885/98678
dc.publisherCold Spring Harbor Laboratory Press
dc.sourceRNA
dc.titleAn extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis
dc.typeJournal article
local.bibliographicCitation.issue12
local.bibliographicCitation.lastpage2118
local.bibliographicCitation.startpage2103
local.contributor.affiliationLin, Ching-Jung, Sloan-Kettering Institute
local.contributor.affiliationSmibert, Peter, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationZhao, Xiaoyu, Stony Brook University
local.contributor.affiliationHu, Jennifer F., Massachusetts Institute of Technology (MIT)
local.contributor.affiliationRamroop, Johnny, The City College of the City University of New York
local.contributor.affiliationKellner, Stefanie M., Massachusetts Institute of Technology (MIT)
local.contributor.affiliationBenton, Matthew, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGovind, Shubha, The City College of the City University of New York
local.contributor.affiliationDedon, Peter C., Massachusetts Institute of Technology (MIT)
local.contributor.affiliationSternglanz, Rolf, Stony Brook University
local.contributor.affiliationLai, Eric C., Sloan-Kettering Institute
local.contributor.authoremailrepository.admin@anu.edu.au
local.contributor.authoruidSmibert, Peter, u3975303
local.contributor.authoruidBenton, Matthew, u4500361
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor060403 - Developmental Genetics (incl. Sex Determination)
local.identifier.absfor060808 - Invertebrate Biology
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
local.identifier.ariespublicationU3488905xPUB6767
local.identifier.citationvolume21
local.identifier.doi10.1261/rna.053934.115
local.identifier.scopusID2-s2.0-84947427227
local.identifier.uidSubmittedByU3488905
local.type.statusPublished Version

Downloads

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
01_Lin_An_extensive_allelic_series_of_2015.pdf
Size:
912.49 KB
Format:
Adobe Portable Document Format
Download

Collections

ANU Research Publications

DSpace software copyright © 2002-2024 LYRASIS