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Investigation of the role of m6A methylation on microRNA biogenesis and arm-switching using zebrafish as biological model.

Grant number: 17/17510-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2018
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Genetics - Animal Genetics
Principal researcher:Danillo Pinhal
Grantee:Arthur Casulli de Oliveira
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


The arm-switching process has notorious impact at gene regulation. This process occurs by the diferential selection between 5p and 3p miRNA arms that will be loaded into miRISC complex during the ontogenetic development, between diferent tissues or even between species. The arm-switching has recognized biological impact, once miRNAs 5p and 3p usually regulate targets with distinct biological process and its desregulation is associated with several types of cancer. In this sense, such arm selection is highly important to provide the right cell signature among tissues. However, until today, the molecular mechanisms involving the arm-switching regulation are unknown. Recently, the m6A methylation was described as an important regulator during miRNA biogenesis, being a recognition site of DROSHA, an enzime responsible for cleave the pri-miRNA and determining the final portion of the mature miRNAs during its biogenesis. Considering that this methylation changes the secondary structure of messenger RNAs (mRNAs) and that the cleavage site promoted by DROSHA depends on the secondary structure of the pri-miRNA, we hypothesize that the m6A methylation may also changes the secondary structure of pri-miRNAs and thus promotes alternative cleavages by DROSHA. Knowing that the arm-selection occurs due to the instability of the 5' portions of the mature miRNAs, these alternative cleavages may be responsible for the events of arm-switching. In order to test this hypotesis, we propose to analyse the arm-switching and m6A methylation patterns using the Danio rerio (zebrafish) as biological model. Moreover, we will evaluate the potential influence of the m6A methylation on arm selection by the knockout of methylation sites and quantification of 5p and 3p expression. These experiments will amplify the knowledge about miRNA biogenesis and its regulatory activities during the development of the vertebrates.

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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)
OLIVEIRA, UR C.; BOVOLENTA, LUIZ A.; ALVES, LUCAS; FIGUEIREDO, LUCAS; RIBEIRO, AMANDA O.; CAMPOS, VINICIUS E.; LEMKE, NEY; PINHAL, DANILLO. Understanding the Modus Operandi of MicroRNA Regulatory Clusters. CELLS, v. 8, n. 9, . (18/05484-0, 18/26409-6, 12/13450-1, 12/15589-7, 15/19176-7, 17/17510-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
OLIVEIRA, Arthur Casulli de. Investigation of the biological function of microRNA arm switching events and their potential association with the RNA methylation m6A using zebrafish as model organism. 2021. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.

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