Anti-U1A monoclonal antibodies recognize unique epitope targets of U1A which are involved in the binding of U1 RNA.

Published

Journal Article

The U1A (or nRNP A) protein is known to play a critical role in eukaryotic pre-mRNA splicing and polyadenylation. Previous studies revealed that several mouse monoclonal antibodies (MAbs) recognized U1A as part of the U1snRNP, while MAb 12E12 was unique in that it recognized an epitope that is masked when U1A is bound to U1 RNA. In order to further characterize and understand the antigenic targets of these MAbs, we undertook fine specificity epitope mapping studies. Anti-U1A MAbs 12E12 and 10E3 each recognize unique peptides from the U1A protein. Interestingly, these MAbs recognize epitopes which have been shown to be antigenic in human autoimmune diseases. When superimposed on structures of U1A derived from crystal and NMR data, the major epitope recognized by 12E12 (amino acids 103-108) localizes to the surface of the U1A molecule. The 12E12 epitope is immediately adjacent to a helix which probably reacts to U1 RNA binding by undergoing a conformational change. This modification of structure effectively masks the 12E12 epitope, thus preventing binding of the monoclonal to U1A/U1 RNA complexes. These findings suggest that the structure of the U1A protein may be different when not part of the U1snRNP.

Full Text

Duke Authors

Cited Authors

  • Lutz, CS; McClain, MT; Harley, JB; James, JA

Published Date

  • May 2002

Published In

Volume / Issue

  • 15 / 3

Start / End Page

  • 163 - 170

PubMed ID

  • 12203842

Pubmed Central ID

  • 12203842

International Standard Serial Number (ISSN)

  • 0952-3499

Digital Object Identifier (DOI)

  • 10.1002/jmr.569

Language

  • eng

Conference Location

  • England