Integrated tRNA, transcript, and protein profiles in response to steroid hormone signaling

Abstract

The accurate and efficient transfer of genetic information into amino acid sequences is carried out through codon-anticodon interactions between mRNA and tRNA, respectively. In this way, tRNAs function at the interface between gene expression and protein synthesis. Whether tRNA levels are dynamically regulated and to what degree tRNA abundance influences the cellular proteome remains largely unexplored. Here we profile tRNA, transcript and protein levels in Drosophila Kc167 cells, a plasmatocyte cell line that, upon treatment with 20-hydroxyecdysone, differentiates into macrophages. We find that high abundance tRNAs associate with codons that are overrepresented in the Kc167 cell proteome, whereas tRNAs that are in low supply associate with codons that are underrepresented. Ecdysone-induced differentiation of Kc167 cells leads to changes in mRNA codon usage in a manner consistent with the developmental progression of the cell. At both early and late time points, ecdysone treatment concomitantly increases the abundance of tRNAThr(CGU), which decodes a differentiation-associated codon that becomes enriched in the macrophage proteome. These results together suggest that tRNA levels may provide a meaningful regulatory mechanism for defining the cellular proteomic landscape.

Topological organization and dynamic regulation of human tRNA genes during macrophage differentiation

“…The dynamic expression of individual tRNA genes during cellular differentiation supports a more complicated structure governing nascent tRNA levels than simply tDNA copy number. Instead, differential transcription of human tRNA genes may provide a system for refining cellular tRNA pools towards cell-type-specific demands, consistent with recent examples of tRNA dynamics in response to specific perturbations [ 4 , 5 , 99 ]. In THP-1 cells, the decrease in nascent tRNA levels is likely harmonized with a slow-down in biosynthesis, as differentiation is accompanied by a loss in cellular proliferation and decreasing levels of regulatory kinases that control entry and progression through the cell cycle [ 100 , 101 ].…”

Ecdysone-Induced 3D Chromatin Reorganization Involves Active Enhancers Bound by Pipsqueak and Polycomb

“…To this end, we examined changes in Psq and Pc interactions during the response to the steroid hormone 20-hydroxyecdysone (20-HE) (D’Avino and Thummel, 2000). Treatment of Drosophila macrophage-like Kc167 cells with 20-HE triggers their differentiation, recapitulating events occurring during metamorphosis (Van Bortle et al, 2015). Visual inspection of ChIP-seq data indicates the presence of Psq S peaks at genes induced by 20-HE, suggesting that Psq may be involved in the response to this hormone.…”

Pool-GWAS on reproductive dormancy in Drosophila simulans suggests a polygenic architecture

“…Inositol 1,4,5-triphosphate kinase 2 ( IP3K2 ; chromosome X) harbored 3 candidate SNPs in its 5′UTR ( P -value ≥ 8.59e-16). It is regulated by ecdysteroids ( Van Bortle et al 2015 ) and participates in cold acclimation ( MacMillan et al 2016 ) and apoptotic/autophagic cell death ( Terhzaz et al 2010 ; Nelson et al 2014 ) in D. melanogaster . Cell death is of particular interest, as this process is an integral part of the mid-oogenesis checkpoint that blocks oogenesis under dormancy-inducing conditions ( Lirakis et al 2018 ).…”