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Identification of factors responsible for translational regulation in neuronal differentiation

Grant number: 16/23120-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2017
Effective date (End): May 31, 2018
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Mário Henrique Bengtson
Grantee:Denis Bruno Santos Marques Nunes
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/21704-9 - Impact of translational regulation into the neural differentiation, AP.JP

Abstract

During cell differentiation, several mechanisms are used by cells to warranty that genes are expressed in the right time and in the right level, modulating the multiple pathways involved on this complex process. One of these mechanisms controls which specific mRNAs and in what rate will be translated by the ribosome, and it is known as translation control of gene expression. Since some time ago, it has being known that this mechanism should be fundamental to cell functioning, considering that protein expression poorly correlates with mRNA expression. Despite this, we lack fundamental understanding of which are all the factor that participate on this process, how it operates and which pathways are modulated by it. On this project, we propose to try to understand how translation control participates in the neural differentiation of stem cells. We want to identify genes and pathways regulated by this process and the possible proteins/miRNA participating in the mechanism. To this aim, we propose to compare the global levels of each mRNA expressed (RNAseq) with global levels of each corresponding mRNA bound to ribosomes (Riboseq) in different time points of neural differentiation induction. This would allow for instances, the identification of genes whose mRNA expression doesn't change, but whose translation rate is controlled during differentiation. The miRNA and RNA biding proteins expression levels will be compared in the same time points in search of possible players in the process. We will use cell and biochemistry assays and bioinformatics to determine the impact of the translation control on the differentiation process. (AU)

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