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

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

doi:10.3390/ijms22052396

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.

Highlights

Lifespan is determined by the processes that occur at the molecular, cellular, tissue, and organism levels, as well as the influence of damaging environmental factors and other external conditions
The median lifespan was reproducibly higher in males and females with piwi knockdown in the nervous system and in the fat body compared with flies without induction of RNA interference (Figure 2e,f, Table S1)
Since the positive effect of knockdown of some of the studied Argonaute genes on longevity was manifested in the case of their RNA interference in the nervous system and the fat body, we carried out further research only with these variants

Summary

Introduction

Lifespan is determined by the processes that occur at the molecular, cellular, tissue, and organism levels, as well as the influence of damaging environmental factors and other external conditions. Among the molecular mechanisms of lifespan regulation, epigenetic mechanisms have a special place. A disturbance of epigenetic regulation can lead to cumulative negative consequences associated with the loss of functionality of cells and an organism, a decrease in its adaptive capabilities [1,2]. This is exactly what happens during the aging of an organism, epigenetic alterations are one of the basic hallmarks of aging [3]. There is a change in the structure of chromatin (for example, a loss of nucleosomes and a decrease in the amount of heterochromatin), DNA methylation status, modification of histone marks, changes in the patterns of noncoding

Methods

Results

Conclusion