Functional expression of AGO2: study of the 'core of risc complex' role in retinal development

• Grant number: 17/26388-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Marília Inês Móvio
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs (approximately 20 nucleotides) that control protein levels in post-transcriptional manner by the alignment to complementary target messenger RNA (mRNA). The action of miRNAs depends on mechanisms mediated by RNA-induced silencing complex (RISC), and the knowledge about expression of its components and activity is limited. In this regard, it is particularly interesting the role of Argonaute 2 (AGO2), an essential protein of RISC, which is directly involved in postnatal development due to its importance on cell maturation and proliferation. Therefore, considering the lack of descriptive studies on miRNA-related proteins and AGO2 relevance as well, the main purposes of this project are: 1) to describe the AGO2 accumulation in specific retinal cell types in both developing and adult retina; 2) combining in vivo and in vitro strategies, we intend to determine the role of AGO2 in cell cycle progression; 3) combining pharmacological inhibition and knockdown strategies, we will determine the role of AGO2 in the differentiation of retinal neuronal subtypes. To this end, we will combine molecular biology and cellular approaches as gene silencing using morpholinos, pharmacological intervention, immunofluorescence analysis, real time PCR, western blotting, primary cell cultures and flow cytometry. (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)

MOVIO, MARILIA INES; DE LIMA-VASCONCELLOS, THEO HENRIQUE; DOS SANTOS, GABRIELI BOVI; ECHEVERRY, MARCELA BERMUDEZ; COLOMBO, ELISABETTA; MATTOS, LEONARDO S.; RESENDE, RODRIGO RIBEIRO; KIHARA, ALEXANDRE HIROAKI. Retinal organoids from human-induced pluripotent stem cells: From studying retinal dystrophies to early diagnosis of Alzheimer?s and Parkinson?s disease. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 10-pg., 2023-03-17. (21/14227-3, 21/03711-1, 19/17892-8, 20/02035-0, 20/11667-0, 21/11969-9, 17/26388-6)