Functional characterization of RNA binding proteins Lin28 and Msi1 in neurogenesis

• Grant number: 12/22950-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 01, 2013
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Márcia Cristina Teixeira dos Santos
• Supervisor: Luiz Otavio Ferraz Penalva
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Texas Health Science Center at Houston (UTHealth), United States
• Associated to the scholarship: 11/51588-2 - Functional characterization of the LIN28 protein in tumorigenesis of the central nervous system, BP.PD

Abstract

Neural stem cells are regarded as new therapeutic potential for neurodegenerative diseases and injuries marrow by their ability to self-renew, proliferate and differentiate giving rise to new neural cells able to migrate to areas of injury and replacing damaged tissue. However, understanding the process of differentiation of neural stem cells is crucial to develop new cellular therapies. Changes in gene expression are required for physiological and morphological changes necessary for cell differentiation. Although numerous processes such as chromatin remodeling and transcription regulation being involved, the role of post-transcriptional regulation is absolutely critical. In this context, the activity of miRNAs and the RNA binding proteins has to be emphasized, once that function as key regulators of processes such as RNA processing, splicing, stability, transport and translation. Among the RNA binding proteins involved in neurogenesis, we highlight Musashi1 (Msi1) and Lin28. Both proteins are highly expressed in stem cells and required for self-renewal. The expression of these proteins must be suppressed to neuronal differentiation occurs. Msi1 and Lin28 are involved in miRNA metabolism and regulation of translation. In this project, we intend to investigate the functions of both proteins in neurogenesis using biochemical methods, molecular and genomics. More precisely, we will map genes (targets) regulated by each protein CLIP and methodology to study the integration with protein partners identified by proteomic studies and two-hybrid analysis. The sum of results can elucidate the mechanism of regulation, as well as open new functions of these proteins. (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)

SANTOS, MARCIA C. T.; TEGGE, ALLISON N.; CORREA, BRUNA R.; MAHESULA, SWETHA; KOHNKE, LUANA Q.; QIAO, MEI; FERREIRA, MARCO A. R.; KOKOVAY, ERZSEBET; PENALVA, LUIZ O. F.. miR-124,-128, and-137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network. Stem Cells, v. 34, n. 1, p. 220-232, JAN 2016. (12/22950-8, 11/51588-2, 13/25483-4)