Interleukin-1-inducible MCPIP Protein Has Structural and Functional Properties of RNase and Participates in Degradation of IL-1beta mRNA

FEBS J. 2009 Dec;276(24):7386-99. doi: 10.1111/j.1742-4658.2009.07452.x.

Abstract

In human monocyte-derived macrophages, the MCPIP gene (monocyte chemoattractant protein-induced protein) is strongly activated by interleukin-1beta (IL-1beta). Using bioinformatics, a PIN domain was identified, spanning amino acids 130-280; such domains are known to possess structural features of RNases. Recently, RNase properties of MCPIP were confirmed on transcripts coding for interleukins IL-6 and IL-12p40. Here we present evidence that siRNA-mediated inhibition of the MCPIP gene expression increases the level of the IL-1beta transcript in cells stimulated with LPS, whereas overexpression of MCPIP exerts opposite effects. Cells with an increased level of wild-type MCPIP showed lower levels of IL-1beta mRNA. However, this was not observed when mutant forms of MCPIP, either entirely lacking the PIN domain or with point mutations in this domain, were used. The results of experiments with actinomycin D indicate that lower levels of IL-1beta mRNA are due to shortening of the IL-1beta transcript half-life, and are not related to the presence of AU-rich elements in the 3' UTR. The interaction of the MCPIP with transcripts of both IL-1beta and MCPIP observed in an RNA immunoprecipitation assay suggests that this novel RNase may be involved in the regulation of expression of several genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • Endoribonucleases / metabolism*
  • Gene Expression Regulation
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / physiology
  • Humans
  • Interleukin-1 / physiology*
  • Interleukin-1beta / genetics*
  • Macrophages / metabolism
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism*
  • Ribonucleases
  • Sequence Alignment
  • Tissue Distribution
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • U937 Cells

Substances

  • HNRPD protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Interleukin-1
  • Interleukin-1beta
  • RNA, Messenger
  • Transcription Factors
  • Endoribonucleases
  • Ribonucleases
  • ZC3H12A protein, human