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Hydrolysis by catalytic IgGs of microRNA specific for patients with schizophrenia

Evgeny A Ermakov1,2, Svetlana A Ivanova3, Valentina N Buneva1,2

  • 1Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave., Novosibirsk, Russia.

IUBMB Life
|January 18, 2018
PubMed

Insights

Autoantibodies in 100% of schizophrenia patients show RNase activity, degrading specific microRNAs crucial for gene regulation. These RNase autoantibodies may contribute to schizophrenia pathogenesis.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • The role of autoimmune changes in schizophrenia (SCZ) pathogenesis remains unclear.
  • MicroRNAs (miRNAs) are vital regulators of gene expression implicated in SCZ.

Purpose of the Study:

  • To investigate the presence and activity of autoantibodies in SCZ patients.
  • To determine if these autoantibodies target SCZ-associated microRNAs.

Main Methods:

  • Analysis of autoantibody activity in SCZ patient serum.
  • Site-specific hydrolysis mapping of microRNAs by autoantibodies.
  • Assessment of autoantibody RNase activity against various RNA substrates.

Main Results:

  • Autoantibodies from 100% of SCZ patients exhibited RNase activity.
  • Specific hydrolysis of four SCZ-associated microRNAs (miR-137, miR-9-5p, miR-219-2-3p, miR-219a-5p) was observed.
  • Cleavage sites were predominantly located in microRNA loops or loop-associated duplex regions.

Conclusions:

  • RNase activity of autoantibodies may reduce the regulatory functions of specific microRNAs in SCZ.
  • These RNase autoantibodies could play a role in the development of schizophrenia.
Keywords:
abzymesautoimmune reactionsmicroRNA hydrolysisschizophrenia

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