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#smallRNA

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Public
Aging Highlights

Tissue-specific overexpression of the double-stranded RNA transporter SID-1 limits lifespan in C. elegans

#smallRNA #Celegans #aging

biorxiv.org/content/10.1101/20

bioRxivTissue-specific overexpression of the double-stranded RNA transporter SID-1 limits lifespan in C. elegansIntertissue RNA transport has emerged as a novel signaling mechanism. In C. elegans, this is conferred by the systemic RNAi pathway, in which the limiting step is the cellular import of extracellular RNAs via SID-1. To better understand the physiological role of systemic RNAi in vivo, we modified the function of SID-1 through loss-of-function mutation and tissue-specific overexpression of sid-1 in C. elegans. We observed that sid-1 loss-of-function mutants are as healthy as wild-type worms. Conversely, overexpression of sid-1 in intestine, muscle, or neurons rendered worms short-lived. The effects of intestinal sid-1 overexpression were reversed by silencing the components of the systemic RNAi pathway sid-1, sid-2 and sid-5, thus implicating RNA transport. Moreover, silencing the miRNA biogenesis proteins pash-1 and dcr-1 rendered the lifespan of worms with intestinal sid-1 overexpression similar to controls. Lastly, we observed that the lifespan decrease produced by tissue-specific sid-1 overexpression was dependent on the bacterial food source. Collectively, our data support the notion that systemic RNA signaling is tightly regulated, and unbalancing that process provokes a reduction in lifespan.
Public
Aging Highlights

The small RNA landscape is stable with age in Drosophila

#smallRNA #Drosophila #aging

journals.plos.org/plosone/arti

journals.plos.orgThe small RNA landscape is stable with age and resistant to loss of dFOXO signaling in DrosophilaAging can be defined as the progressive loss of physiological homeostasis that leads to a decline in cellular and organismal function. In recent years, it has become clear that small RNA pathways play a role in aging and aging related phenotypes. Small RNA pathways regulate many important processes including development, cellular physiology, and innate immunity. The pathways illicit a form of posttranscriptional gene regulation that relies on small RNAs bound by the protein components of the RNA-induced silencing complexes (RISCs), which inhibit the expression of complementary RNAs. In Drosophila melanogaster, Argonaute 1 (Ago1) is the core RISC component in microRNA (miRNA) silencing, while Argonaute 2 (Ago2) is the core RISC component in small interfering RNA (siRNA) silencing. The expression of Ago1 and Ago2 is regulated by stress response transcription factor Forkhead box O (dFOXO) increasing siRNA silencing efficiency. dFOXO plays a role in multiple stress responses and regulates pathways important for longevity. Here we use a next-generation sequencing approach to determine the effects of aging on small RNA abundance and RISC loading in male and female Drosophila. In addition, we examine the impact of the loss of dFOXO on these processes. We find that the relative abundance of the majority of small RNAs does not change with age. Additionally, under normal growth conditions, the loss of dFOXO has little effect on the small RNA landscape. However, we observed that age affects loading into RISC for a small number of miRNAs.
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