The nuclear reorganization is related to gene expression

• Grant number: 98/15979-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 1999
• End date: September 30, 2003
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Schenkman
• Grantee: Sergio Schenkman
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

In this project we intend to study how the nuclear reorganization is related to gene expression, since there are many evidences showing that transcription, RNA processing and RNA transport are spatially organized in the cell nucleus. As a model of study we will utilize protozoan parasites of the Trypanosomatidae family (Trypanosoma cruzi and Trypanosoma brucei) as these organisms have a unique mechanism to process messenger RNAs (mRNAs). Most of their mRNAs are constitutively transcribed as long polycistronic messages. After, or concomitant with transcription all precursor RNAs receive at the 5' end a small exogenous sequence from a single type of gene in a process named trans-splicing. Simultaneously a poly-adenosine tail is added to the 3' end. Studies of the space interactions between these events can help us to understand how these processes are coupled. To approach this problem we will realize the following studies:1) Biochemical and morphological characterization of Trypanosoma cruzi nuclei along the development.2) Studies of the chromatin and nuclear matrix organization and their role in T. cruzi gene expression during the parasite differentiation.3) identification and studies on the dynamic of heterochromatin and telomeric regions.4) Identification and characterization of the large subunit of RNA polimerase II of T cruzi.5 )Studies of the role of the carboxy-terminal domain (CTD) of the large subunit of RNA polimerase R in the RNA processing in tripanosomes.6 )Studies of the mechanism of transcription termination/initiation by RNA polimerase II in trypanosomes. (AU)