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Uncovering mechanisms of longevity mediated by mobile RNAs

Grant number: 17/01339-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2017
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Genetics - Animal Genetics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Henrique Camara
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):17/24161-4 - Determining the role of conserved, fat-enriched circulating miRNAs in aging and in triacylglycerol accumulation of Drosophila melanogaster, BE.EP.DR

Abstract

Aging and the consequent increase in the prevalence of chronic diseases is a serious public health issue. These problems have been attracting the attention of governmental agencies and research centers with the aim to propose strategies to promote healthy aging. The RNA interference (RNAi) pathway is among the molecular pathways described as important to control the rate of aging in different species. The RNAi pathway comprises the mechanism of gene silencing exerted by small RNAs, such as miRNAs (microRNAs) and siRNAs (small-interference RNAs). These RNAs act in the cells where they are initially produced and, additionally, act as mobile elements within the organism to silence genes in distant tissues. We have previously demonstrated that mutations in SIDs (Systemic RNA Interference) and RSDs (RNAi Spreading Defective), proteins of the RNA transport machinery, impair a wide range of phenotypes in C. elegans, including longevity and stress resistance, suggesting that mobile RNAs regulate the physiology of these animals. Dietary restriction is an intervention that increases lifespan, promotes stress resistance and up-regulates Dicer - a key enzyme in small RNA biogenesis - in aged mice or C. elegans. In addition, intestinal Dicer overexpression protects worms from heat stress in a matter that is dependent on the RNA transporter SID-1, indicating the involvement of the systemic RNAi pathway. In the present project we will investigate the functions and signaling mechanisms of mobile RNAs in C. elegans. We aim to identify the mobile RNAs that regulate longevity. In addition, we will address the role of components of the RNA transport machinery in the beneficial effects of Dicer overexpression and dietary restriction. Due to their evolutionary conservation, it will be important to comprehend how key proteins in the systemic RNAi pathway control physiological functions in a simpler model organism, which can provide important information in order to elucidate more elaborated mechanisms with fundamental implications in more complex animals. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE-SOUZA, EVANDRO A.; PIMENTEL, FELIPE S. A.; DE-QUEIROZ, ANA LUIZA F. V.; CAMARA, HENRIQUE; FELIX-FORMIGA, MIKAELLA L.; MACHADO, CAIO M.; PINTO, SILAS; GALINA, ANTONIO; MORI, MARCELO A.; MONTERO-LOMELI, MONICA; MASUDA, CLAUDIO A. The yeast protein Ubx4p contributes to mitochondrial respiration and lithium?galactose?mediated activation of the unfolded protein response. Journal of Biological Chemistry, v. 295, n. 12, p. 3773-3782, MAR 20 2020. Web of Science Citations: 0.
DE-SOUZA, EVANDRO A.; CAMARA, HENRIQUE; SALGUEIRO, WILLIAN G.; MORO, RAISSA P.; KNITTEL, THIAGO L.; TONON, GUILHERME; PINTO, SILAS; PINCA, ANA PAULA F.; ANTEBI, ADAM; PASQUINELLI, AMY E.; MASSIRER, KATLIN B.; MORI, MARCELO A. RNA interference may result in unexpected phenotypes in Caenorhabditis elegans. Nucleic Acids Research, v. 47, n. 8, p. 3957-3969, MAY 7 2019. Web of Science Citations: 3.

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