Molecular and cellular basis of the physio(patho)logy associated with the expression of intracellular antigens

Pathophysiology and Therapy of Genetic Diseases
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

The regulation of the heterogeneity of the transcriptome and proteome is key stage on the way to understand differences in the diversity of proteins observed in organisms of similar genetic complexity. The intracellular antigens TIA1 (T-cell intracellular antigen 1) and TIAR/TIAL1 (TIA1 related/like protein) have been involved in the regulation of gene expression on different aspects of the control of RNA metabolism, such as: i) transcription through its interaction with DNA and RNA polymerase II; ii) alternative splicing of pre-mRNA through the selection of atypical 5' splicing sites; iii) localization, stability and/or translation of eukaryotic mRNAs through the interaction with 5' and 3' untranslatable regions; and iv) modulation of biological programmes for cell survival (inflammation, proliferation, apoptosis, cell stress or infections by viruses). As a consequence, the initial hypothesis -of the work line initiated nine years ago- it is that these proteins may play a fundamental role in controlling gene expression by regulating/modulating the dynamics of human transcriptome and proteome, their expression and function, in order to prevent situations which put aberrant cell viability at risk in patho-physiological situations such as stress-associated responses, tumorigenesis or aging and their related diseases. So today, our objective is to characterize the early and late cellular processes and molecular mechanisms in which TIA proteins participate and how they are involved to regulate/modulate cellular homeostasis via preventing the development and/or progression of deleterious phenotypes. Understanding the regulatory dynamics associated with these intracellular antigens could serve as the basis for identifying future therapeutic targets.

Molecular Biomedicine