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. 2020 Mar 31;43(3):304-311.
doi: 10.14348/molcells.2019.0273.

Methionyl-tRNA Synthetase Regulates Lifespan in Drosophila

Yoon Seok Suh  1   2 , Eunbyul Yeom  1 , Jong-Woo Nam  3 , Kyung-Jin Min  3 , Jeongsoo Lee  1   2 , Kweon Yu  1   2   4
Affiliations

Methionyl-tRNA Synthetase Regulates Lifespan in Drosophila

Yoon Seok Suh et al. Mol Cells. .

Abstract

Methionyl-tRNA synthetase (MRS) is essential for translation. MRS mutants reduce global translation, which usually increases lifespan in various genetic models. However, we found that MRS inhibited Drosophila reduced lifespan despite of the reduced protein synthesis. Microarray analysis with MRS inhibited Drosophila revealed significant changes in inflammatory and immune response genes. Especially, the expression of anti-microbial peptides (AMPs) genes was reduced. When we measured the expression levels of AMP genes during aging, those were getting increased in the control flies but reduced in MRS inhibition flies agedependently. Interestingly, in the germ-free condition, the maximum lifespan was increased in MRS inhibition flies compared with that of the conventional condition. These findings suggest that the lifespan of MRS inhibition flies is reduced due to the down-regulated AMPs expression in Drosophila.

Keywords: Drosophila; anti-microbial peptides; lifespan; methionyl-tRNA synthetase.

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Conflict of interest statement

Disclosure

The authors have no potential conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. Evolutionary conserved domains of Drosophila MRS, the efficacy of GeneSwitch system, and protein translation in MRS inhibition flies.
(A) Evolutionary conserved domains between human MRS and Drosophila MRS. (B) GFP protein level was highly elevated in ActinGS > GFP flies with RU486 20 μg/ml (RU+). (C) MRS mRNA expression was getting reduced in ActinGS > MRS RNAi flies RU dose dependently. (D) Protein translation level marked by the phosphorylated S6K protein was reduced in MRS inhibition flies RU dose dependently. (E) Global translation marked by puromycin incorporation was reduced in MRS inhibition flies RU dose dependently. RU 0.2, RU 2, and RU 20: ActinGS > MRS RNAi with RU486 0.2 μg/ml, 2 μg/ml, 20 μg/ml, respectively. Data are presented as mean ± SEM; *P < 0.05 and **P < 0.01.
Fig. 2
Fig. 2. Lifespan in MRS inhibition flies.
(A) The lifespan of MRS inhibition flies were reduced RU dose dependently. (B) Statistic table of lifespan analysis. RU 0.2, RU 2, and RU 20: ActinGS > MRS RNAi with RU486 0.2 μg/ml, 2 μg/ml, 20 μg/ml.
Fig. 3
Fig. 3. MRS regulates inflammatory and immune response genes.
(A) Gene ontology graph from the microarray analysis with 30 days old MRS inhibition flies showed that the genes involved in inflammatory and immune responses were changed significantly. (B) Microarray analysis showed that the mRNA expression of AMPs (attA, cecA, Def, DptA, Drs, Dro, and MTK) were down-regulated in 30 days old MRS inhibition flies.
Fig. 4
Fig. 4. Expression of AMPs is reduced by aging in MRS inhibition flies.
(A) In the control (ActinGS > MRS RNAi, RU–), the mRNA expression levels of AMPs (attA, cecA, Def, DptA, Drs, Dro, and MTK) were increased during aging. (B) In MRS inhibition flies (ActinGS > MRS RNAi, RU+), the mRNA expression levels of AMPs (attA, cecA, Def, DptA, Drs, Dro, and MTK) were reduced by aging. RU+, ActinGS > MRS RNAi with RU486 20 μg/ml. Data are presented as mean ± SEM; *P < 0.01, **P < 0.01, and ***P < 0.001. N.S., statistically not significant.
Fig. 5
Fig. 5. The lifespan of MRS inhibition flies is increased in the germ-free condition.
(A) The maximum lifespan of MRS inhibition flies was increased in the germ-free condition (ActinGS > MRS RNAi, RU+; red dotted line) compared with that of the conventional condition (ActinGS > MRS RNAi, RU+; red solid line). (B) Statistic table of lifespan analysis of Fig. 5A. (C) The maximum lifespan of control flies did not increase in the germ-free condition (ActinGS > MRS RNAi, RU–, dotted line) compared with that of the conventional condition (ActinGS > MRS RNAi, RU–, solid line). (D) Table of lifespan analysis of Fig. 5C. RU–, ActinGS > MRS RNAi without RU486.
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