Identification of molecular pathways translationally regulated in neuronal differentiation

• Grant number: 15/21433-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2016
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mário Henrique Bengtson
• Grantee: Érico Luiz Moreto Lins
• Host 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 cellular differentiation, multiple biochemical mechanisms are employed by the cell to ensure that genes are being expressed at the right time and in sufficient levels, regulating properly many pathways involved in this complex process. One of this mechanisms controls which mRNAs specifically and the levels that they will be translated by the ribosomes, which it is known as translational control of gene expression. It is known that this mechanism should be essential to cellular functioning, since protein expression shows weak correlation with mRNA expression. However, the factors that control this mechanism, how it works and which pathways are regulated by them are still unknown. In the young researcher project, we propose understand how translation regulations of gene expression contribute to neuronal differentiation of neuroprogenitor cells. We want to understand which genes and pathways are translationally regulated in the differentiation process and which proteins/miRNAS participate of this regulation. To achieve this, we propose to compare global levels of each cell mRNA gene expressions (RNA-seq library) with the level of the underlying mRNA bound to the ribosomes (Ribo-seq library) at different time-points of the neuronal differentiation. We will search for genes which translation levels are changed during differentiation as a regulation control mechanism (e.g. genes which have stable mRNA expression but the mRNA fraction bound to the ribosome being altered during differentiation). Comparison among libraries allows identify each genes are translationally regulated during the differentiation process. Furthermore, miRNAs and RNA-binding proteins expression will be compared at the same time-point to suggest possible regulators. Alterations of the translation efficiency will be correlated with induction/repression of miRNAs and RNA-binding proteins, suggesting new ways of regulation. This will be experimentally validated through inhibition of these factors and verification of lacking of regulation, besides the detection of the physical interaction of the regulated mRNA and these same factors. Finally, we will perform biological assays and bioinformatics to determine the impact of the regulation in the differentiation process. We will verify if the interference with the translation control process inhibit totally/partially the differentiation process. In this project, we propose construct the RNAseq, miRNAseq and Riboseq libraries and confirm the translation regulation of the discovered genes, comparing RNAseq and Riboseq libraries. (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)

LINS, ERICO MORETO; OLIVEIRA, NATASSIA CRISTINA MARTINS; REIS, OSVALDO; FERRASA, ADRIANO; HERAI, ROBERTO; MUOTRI, ALYSSON R.; MASSIRER, KATLIN BRAUER; BENGTSON, MARIO HENRIQUE. Genome-wide translation control analysis of developing human neurons. MOLECULAR BRAIN, v. 15, n. 1, p. 15-pg., 2022-06-15. (14/21704-9, 14/50897-0, 15/21433-8)

MARTINS OLIVEIRA, NATASSIA CRISTINA; LINS, ERICO MORETO; MASSIRER, KATLIN BRAUER; BENGTSON, MARIO HENRIQUE. Translational Control during Mammalian Neocortex Development and Postembryonic Neuronal Function. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 114, p. 11-pg., 2021-05-20. (15/21433-8)

MARTINS OLIVEIRA, NATASSIA CRISTINA; LINS, ERICO MORETO; MASSIRER, KATLIN BRAUER; BENGTSON, MARIO HENRIQUE. Translational Control during Mammalian Neocortex Development and Postembryonic Neuronal Function. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 114, n. SI, p. 36-46, JUN 2021. (15/21433-8, 14/21704-9)