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Biogenesis control of induced pluripotent stem Cells-Specific microRNAs

Grant number: 13/00477-1
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): April 01, 2013
Effective date (End): July 31, 2013
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Robson Francisco Carvalho
Grantee:Carlos Augusto Barnabe Alves
Supervisor abroad: Gracjan Michlewski
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Local de pesquisa : University of Edinburgh, Scotland  
Associated to the scholarship:12/10539-1 - Gene expression kinetics of muscle-specific micro-RNAs (miR-1, miR-133, and miR-206) and atrogenes (Murf1 and MAFBx) in cells treated in vitro with TNF-alpha and INF-gamma, BP.IC

Abstract

Micro-RNAs (miRNAs, miR) are small noncoding RNAs regulators with size ranging from 17 to 25 nucleotides. Currently, more than 21,000 miRNAs from 193 species were recorded, and humans are known 2042. In the nucleus, the pri-miRNA is processed to pre-miRNA by the enzyme RNase III (Drosha), which requires the protein DGCR8 (DiGeorge Syndrome critical region gene 8). The DGCR8/Drosha form a large complex known as Microprocessor complex that recognizes and cleaves the pri-miRNA molecule resulting in a pre-miRNA hairpin structure. After nuclear processing each pre-miRNAs is exported to the cytoplasm by Exportin 5 (EXP5), where is converted by Dicer into miRNAs duplex. After cleavage by Dicer, one strand of this double-stranded RNA is associated with Ago protein to form a RNA-Induced Silencing Complex (RISC) while the other strand is degraded. The identification of miRNAs has opened up a new field of investigation to understand the molecular mechanisms of the regulation of their own biogenesis. An important discovery suggested that the action of several miRNAs can reprogram somatic cells into induced Pluripotent Stem (iPS) cells, suggesting that these miRNAs could play a significant role in iPS cells. The miR-302 family have been shown to be able to directly reprogram mature human fibroblasts into iPS cells. The aim of the project is to analyze the mechanisms behind the biogenesis control of iPS cell-specific miR-302 in selected mouse and human cellular models. The hypothesis is that regulation of miRNA biogenesis pathways in eukaryotic cells is widespread, allowing for rapid and global adaptation of the gene expression machinery to internal and external stimuli. (AU)