The role of the RNA exosome complex during the differentiation of the mouse embryonic stem cells into neural precursor cells

• Grant number: 22/05163-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 01, 2022
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Carla Columbano de Oliveira
• Grantee: Luiz Henrique de Santana Maniero
• Supervisor: Kristopher Brannan
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Houston Methodist Research Institute (HMRI), United States
• Associated to the scholarship: 18/17562-5 - Characterization of neuronal proteins that interact with the EXOSC8 (Rrp43) subunit of the exosome and regulate its activity, BP.DD

Abstract

Regulation of the expression of genes essential for development is mediated by the correct metabolism of RNAs and the exosome, a highly conserved ribonuclease in eukaryotes, is involved in processing, maturation, and quality control of several classes of RNAs. Altering amino acids in the structure of the exosome subunits and their consequent loss of function in RNA processing can cause specific diseases in humans according to the affected subunit. Amino acid changes in the human subunits, EXOSC1, EXOSC2, EXOSC3 EXOSC5, EXOSC8, and EXOSC9 result in clinical manifestations that are similar to pontocerebellar hypoplasia type 1c, an autosomal recessive neurodegenerative disease, characterized by deficit psychomotor, cerebellum and corpuscle hypoplasia, hypomyelination and spinal muscular atrophy since birth. In numerous model organisms, most of the exosome genes were considered essential for life. However, many questions about its specificity in diverse cellular contexts, tissues and/or cells in higher eukaryotes remain unresolved. Therefore, this BEPE-DD proposal aims to improve the knowledge about the RNA exosome complex during the neurodevelopmental stages through the transcriptome-wide target and ribosome association analysis at single-cell resolution. (AU)