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Analysis of gene expression PCBP1, PCBP2 and hnRNP-D and its relationship with alpha and beta thalassemia

Grant number: 11/02037-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2011
Effective date (End): December 31, 2011
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Anderson Ferreira da Cunha
Grantee:Tainá Regina Damaceno Silveira
Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

mRNA turnover is an essential regulatory element of gene expression and is strongly influenced by ribonucleoprotein (RNP) complexes which form on the mRNAs. Studies of human alpha globin mRNA stability have showed a specific RNA complex which forms on the 3`untranslated region of the mRNA supposing to regulate the erythrocyte specific accumulation of alpha globin mRNA. Poly(C) binding activity is one of the protein activities in this multiprotein complex which consists, in the foreground, of two proteins: PCBP1 and PCBP2. Binding the alpha globin 3`UTR cannot be done for these proteins, individually or as a pair, unless they are combined with the remaining non – poly(C) binding proteins of the alpha complex. Recent studies have identified a second proteins group which is part of this alpha globin mRNA alpha complex. Such proteins are known as hnRNPDs and are also involved in decay of mRNA regulated by rich adenine and uracil regions (AREs). Some studies showed that the interaction of HNRNPD is more efficient to PCBP1 than to PCBP2 both in vitro and in vivo, suggesting that HNRNPD could be a remarkable mRNA turnover element participating in the decay and stabilization of mRNA. In a recent study of global gene expression in cells of thalassemic patients, we have found that the PCBP2 gene was differentially expressed when compared to controls, suggesting a possible regulatory role of this gene in this disease. As the encoded protein by this gene is part of the complex cited above, the objective of this work is assess the expression of genes PCBP1, PCBP2 and HNRNPD in reticulocytes of beta thalassemic patients and compare this expression with healthy controls and sickle cell anemia patients, aiming to establish better the role of these proteins in globins genes regulation. (AU)