RNA Polymerase I Polypeptides in Murine Lupus

Rose, Kathleen

Abstract

Rheumatic autoimmune diseases are characterized by the presence of hyperactive B lymphocytes. These cells produce antibodies targeted against a number of nuclear compounds associated with cell proliferation. One of the key components involved in regulation of cell growth is RNA polymerase I, the enzyme responsible for the synthesis of ribosomal RNA (rRNA). Since the activity and concentration of this complex enzyme (eight polypeptides), as well as the rate of rRNA synthesis, are elevated in proliferating cells, these parameters serve as good markers for cell growth. The hypothesis of this project is that, in rheumatic autoimmune disease, events regulating proliferation of cells of the immune system (or their precursors) are altered and that this modification plays a role in the disease. The availability of an animal model (NZB mice) closely approximating the human disease provides the opportunity to test this hypothesis. The goals of this research project are (1) to obtain fundamental information of the control of rRNA synthesis and cell proliferation in lymphoid/hematopoietic cells of normal mice, (2) to establish whether the regulation of rRNA synthesis and expression of RNA polymerase I-associated polypeptides are altered in lymphoid-hematopoietic cells of mice genetically disposed to autoimmune disease, and (3) to elucidate whether RNA polymerase I-associated polypeptides themselves play a role in development of disease.