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Determination of factors that controls Dicer expression in vivo in C. elegans

Grant number: 14/10814-8
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2014
Effective date (End): August 31, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Evandro Araújo de Souza
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):16/02207-0 - Identification of soma-germline interactions that may influence lifespan in Caenorhabditis elegans, BE.EP.MS


Aging increases the risk of chronic diseases, being slowed by caloric restriction. Our group and coworkers identified that, in a conserved way, the synthesis of microRNAs decrease with aging, being reverted by caloric restriction. This phenomenon is a consequence of the regulation of the expression of key enzymes of the microRNA processing pathway, particularly Dicer, which cleaves pre-miRNA in mature microRNA. In mammals, these effects have been observed only in adipose tissue. In C. elegans, it is not yet known in which tissues Dicer suffers a major regulation, though it is known that its expression reduces with aging and increases with caloric restriction. We therefore aim to identify, in a tissue-specific manner, how Dicer is regulated in C. elegans under these situations. Commonly used methods have limitations to answer these questions. Real time PCR and Western Blot consider only the whole body expression; while gene reporter extrachromosomal constructs may be randomly propagated in the cells and/or lost after generations. To overcome these limitations, we will integrate to the genome of C. elegans a construct in which the Dicer gene, under the Dicer promoter, codes a protein fused to GFP. Using microscopic analysis we will validate this model under known situations that stimulate Dicer (i.e., caloric restriction and aging). We will then identify in which tissues Dicer is modulated and test genes involved in this modulation. These data would impact our understanding about the biology of aging, since they could outline a fundamental mechanism that would determine the effects of caloric restriction. (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.; 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.
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.; PARMIGIANI, RAPHAEL B.; WURTELE, MARTIN; MASSIRER, KATLIN B.; MORI, MARCELO A. Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis. REDOX BIOLOGY, v. 18, p. 84-92, SEP 2018. Web of Science Citations: 6.
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. Web of Science Citations: 6.

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