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. 2021 Feb 27;22(5):2396.
doi: 10.3390/ijms22052396.

Tissue-Specific Knockdown of Genes of the Argonaute Family Modulates Lifespan and Radioresistance in Drosophila Melanogaster

Ekaterina Proshkina  1 , Elena Yushkova  1 , Liubov Koval  1 , Nadezhda Zemskaya  1 , Evgeniya Shchegoleva  1 , Ilya Solovev  1   2 , Daria Yakovleva  1   2 , Natalya Pakshina  1 , Natalia Ulyasheva  1 , Mikhail Shaposhnikov  1 , Alexey Moskalev  1   3
Affiliations

Tissue-Specific Knockdown of Genes of the Argonaute Family Modulates Lifespan and Radioresistance in Drosophila Melanogaster

Ekaterina Proshkina et al. Int J Mol Sci. .

Abstract

Small RNAs are essential to coordinate many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of the mutagenic transposon activity. These processes determine the aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in regulating lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters are reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system causes a lifespan increase. But changes in radioresistance depend on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allow us to determine associated molecular mechanisms.

Keywords: Agronaute; Drosophila melanogaster; aging; ionizing radiation; lifespan; piwi; radioresistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Influence of AGO1 (a–d) and AGO2 (e–h) knockdown in the nervous system (a,e) (two replicates combined), fat body (b,f) (two replicates combined), guts (c,g), muscles (d,h) on the survival of Drosophila melanogaster. Differences between survival curves of flies with Argonaute genes’ knockdown (RU486+) and without knockdown (RU486-) are statistically significant with * p < 0.05, ** p < 0.01, *** p < 0.001 (Kolmogorov–Smirnov test).
Figure 2
Figure 2
Influence of AGO3 (a–d) and piwi (e–h) knockdown in the nervous system (a,e) (two replicates combined), fat body (b,f) (two replicates combined), guts (c,g), muscles (d,h) on the survival of Drosophila melanogaster. Differences between survival curves of flies with PIWI genes’ knockdown (RU486+) and without knockdown (RU486-) are statistically significant with * p < 0.05, ** p < 0.01, *** p < 0.001 (Kolmogorov–Smirnov test).
Figure 3
Figure 3
Influence of AGO1 (a,b), AGO2 (c,d), AGO3 (e, f), piwi (g,h) knockdown in the nervous system (a,c,e,g) and fat body (b,d,f,h) on the survival of Drosophila flies after γ-irradiation at the dose of 700 Gy. Differences between survival of flies curves with Argonaute knockdown (RU486+) and without knockdown (RU486-) are statistically significant with * p < 0.05, ** p < 0.01, *** p < 0.001 (Kolmogorov–Smirnov test).
Figure 4
Figure 4
Age-related changes in the expression of Argonaute genes (a,b), transposable elements (c,d), and stress response genes (e,f) in wild-type Canton-S males (a,c,e) and females (b,d,f). Differences between relative expression levels of the investigated genes at the age of 2 weeks and at the ages of 6 and 10 weeks are statistically significant with * p < 0.05 (Mann-Whitney U-test).
Figure 5
Figure 5
Changes in the expression of retrotransposons in irradiated and unirradiated males (a,c,e,g) and females (b,d,f,h) with AGO1 (a–d) and AGO2 (e–h) knockdown. Differences between relative expression levels of retrotransposons of unirradiated flies without Argonaute genes’ knockdown (RU486-, 0Gy) and each of other experimental variants are statistically significant with * p < 0.05 (Mann-Whitney U-test).
Figure 6
Figure 6
Changes in the expression of retrotransposons in irradiated and unirradiated males (a,c,e,g) and females (b,d,f,h) with AGO3 (a–d) and piwi (e–h) knockdown. Differences between relative expression levels of retrotransposons of unirradiated flies without PIWI genes’ knockdown (RU486-, 0Gy) and each of other experimental variants are statistically significant with * p < 0.05 (Mann-Whitney U-test).
Figure 7
Figure 7
Changes in the expression of stress response genes in irradiated and unirradiated males (a,c,e,g) and females (b,d,f,h) with AGO1 (a–d) and AGO2 (e–h) knockdown. Differences between relative expression levels of the investigated genes of unirradiated flies without Argonaute genes’ knockdown (RU486-, 0Gy) and each of other experimental variants are statistically significant with * p < 0.05 (Mann-Whitney U-test).
Figure 8
Figure 8
Changes in the expression of stress response genes in irradiated and unirradiated males (a,c,e,g) and females (b,d,f,h) with AGO3 (a–d) and piwi (e–h) knockdown. Differences between relative expression levels of the investigated genes of unirradiated flies without PIWI genes’ knockdown (RU486-, 0Gy) and each of other experimental variants are statistically significant with * p < 0.05 (Mann-Whitney U-test).
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