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Related Experiment Videos

Autoimmune epitopes in messenger RNA.

Barbara D Lipes1, Jack D Keene

  • 1Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

RNA (New York, N.Y.)
|June 29, 2002
PubMed
Summary

Autoimmune disorders can trigger autoantibodies against messenger RNAs (mRNAs), even though these molecules are typically unstable. This study identified specific RNA structures in mRNAs that elicit immune responses in patients.

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Area of Science:

  • Immunology
  • Molecular Biology
  • RNA Biology

Background:

  • Patients with autoimmune disorders produce autoantibodies targeting RNA molecules.
  • The reactivity against abundant, stable RNAs like U1 snRNA and ribosomal RNA is known, but the basis for reactivity with less abundant, less stable messenger RNAs (mRNAs) is unclear.

Purpose of the Study:

  • To investigate the existence and molecular basis of RNA epitopes in messenger RNAs (mRNAs).
  • To determine if messenger RNAs (mRNAs) can elicit autoantibody responses in patients with autoimmune disorders.

Main Methods:

  • Iterative selection and amplification using pooled patient sera to identify reactive mRNA species.
  • Cloning, sequencing, deletion, and site-directed mutagenesis to characterize specific RNA epitopes.
  • Immunoprecipitation of native mRNAs using identified autoantibodies.

Main Results:

  • Identified discrete RNA epitopes within messenger RNAs (mRNAs).
  • One autoantibody recognized epitopes in mRNAs encoding alternative splicing factor (ASF/SF2) and calmodulin.
  • The epitope was mapped to a 17-base stem-loop structure common to both mRNAs.
  • Demonstrated that messenger RNAs (mRNAs) can be immunoprecipitated by autoantibodies.

Conclusions:

  • Messenger RNAs (mRNAs), despite their instability and low abundance, can elicit autoantibody responses.
  • Direct presentation of RNA structures is a plausible model for generating conformation-specific autoantibodies in autoimmune diseases.

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