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Characterization of neuronal proteins that interact with the EXOSC8 (Rrp43) subunit of the exosome and regulate its activity

Grant number: 18/17562-5
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2019
Effective date (End): December 31, 2024
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Carla Columbano de Oliveira
Grantee:Luiz Henrique de Santana Maniero
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/06477-9 - Functional study of the components of the Saccharomyces cerevisiae exosome and the spliceosome, and their role in posttranscriptional control of gene expression, AP.TEM
Associated scholarship(s):22/05163-4 - The role of the RNA exosome complex during the differentiation of the mouse embryonic stem cells into neural precursor cells, BE.EP.DD

Abstract

Differentiation and neuronal migration are important processes during development, therefore defects related to these steps cause different types of neuronal diseases. 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 various organisms, 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 subunit EXOSC8 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 the birth. This study aims to characterize the neuronal proteins that interact with the EXOSC8 subunit of the human exosome and that may regulate the activity of this complex in the control of gene expression. (AU)

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