Phenotypic screen of nematodes C. elegans mutants for proteins necessary to systemic RNAi

• Grant number: 15/04264-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2015
• End date: February 28, 2017
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Henrique Camara
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction, AP.JP

Abstract

Aging and the consequent increase in the prevalence of chronic diseases are serious public health issues. These problems have been attracting the attention of governmental agencies and research centers with the aim to propose strategies to promote healthy aging. Among the molecular pathways described as important to control the rate of aging in different species, there is the RNA interference pathway (RNAi). RNAi pathway comprises the gene silencing exerted by small RNAs, such as miRNAs (microRNAs) and siRNAs (small-interference RNAs). Our previous data indicate that nematode C. elegans with a loss-of-function mutation within the sid-1 (Systemic RNA Interference Defective) gene, which encodes a double-stranded RNA carrier, have shorter lifespan when subjected to heat stress. Furthermore, the increased thermotolerance of worms overexpressing Dicer, a key enzyme in the biogenesis of small RNAs, is blocked when SID-1 function is abrogated. SID-1 is part of a larger group of proteins necessary for systemic RNAi, i.e. the SIDs and RSDs (RNAi Spreading Defective). Correlations between these proteins and the stress response and aging pathways remain scarce. Although conserved in different species, no physiological functions have been described to SIDs or RSDs, despite their function on the silencing mechanism by exogenous double-stranded RNAs. We will therefore perform phenotypic screens in C. elegans with loss-of-function mutations in SID and RSD genes in order to determine the pathophysiological roles of these proteins in the context of aging, stress response, development and fertility. Due to their evolutionary conservation, it will be important to comprehend how SIDs and RSDs control physiological functions in a simpler model, which can provide important information in order to elucidate more elaborated mechanisms with fundamental implications in more complex organisms. (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)

PINTO, SILAS; SATO, VITOR N.; DE-SOUZA, EVANDRO A.; FERRAZ, RAFAEL C.; CAMARA, HENRIQUE; PINCA, ANA PAULA F.; MAZZOTTI, DIEGO R.; LOVCI, MICHAEL T.; TONON, GUILHERME; LOPES-RAMOS, CAMILA M.; et al. Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis. REDOX BIOLOGY, v. 18, p. 84-92, SEP 2018. (12/04064-0, 15/04264-8, 17/04377-2, 15/01316-7, 14/10814-8, 17/01184-9, 12/24490-4, 10/52557-0, 14/25270-3, 14/25068-0)

FERRAZ, RAFAEL C.; CAMARA, HENRIQUE; DE-SOUZA, EVANDRO A.; PINTO, SILAS; PINCA, ANA PAULA F.; SILVA, RICHARD C.; SATO, VITOR N.; CASTILHO, BEATRIZ A.; MORI, MARCELO A.. IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans. BMC Biology, v. 14, OCT 7 2016. (10/52557-0, 15/01316-7, 12/24490-4, 14/25270-3, 14/10814-8, 14/17145-4, 09/52047-5, 15/04264-8, 12/04064-0, 14/25068-0)