Cell death inhibiting RNA (CDIR) derived from a 3′-untranslated region binds AUF1 and heat shock protein 27

Ksenya Shchors, Fruma Yehiely, Rupinder K. Kular, Kumar U. Kotlo, Gary Brewer, Louis P. Deiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Regulators of programmed cell death were previously identified using a technical knockout genetic screen. Among the elements that inhibited interferon-γ-induced apoptosis of HeLa cells was a 441-nucleotide fragment derived from the 3′-untranslated region (UTR) of KIAA0425, a gene of unknown function. This fragment was termed cell death inhibiting RNA (CDIR). Deletion and mutation analyses of CDIR were employed to identify the features required for its anti-apoptotic activity. Single nucleotide alterations within either copy of the duplicated U-rich motif found in the CDIR sequence abolished the anti-apoptotic activity of CDIR and altered its in vitro association with a protein complex. Further analysis of the CDIR-binding complex indicated that it contained heat shock protein 27 (Hsp27) and the regulator of mRNA turnover AUF1 (heterogeneous nuclear ribonucleoprotein D). In addition, recombinant AUF1 bound directly to CDIR. Furthermore, expression of another AUF1-binding RNA element, derived from the 3′-UTR of c-myc, inhibited apoptosis. We also demonstrate that the level and the stability of p21waf1/Cip1/sdi1 mRNA, a target of AUF1 with anti-apoptotic activity, were increased in CDIR-transfected cells. The level of mRNA and protein of Bcl-2, another anti-apoptotic gene, containing an AUF1 binding site in its 3′-UTR was also increased in CDIR-transfected cells. Our data suggest that AUF1 regulates apoptosis by altering mRNA turnover. We propose that CDIR inhibits apoptosis by acting as a competitive inhibitor of AUF1, preventing AUF1 from binding to its targets.

Original languageEnglish (US)
Pages (from-to)47061-47072
Number of pages12
JournalJournal of Biological Chemistry
Volume277
Issue number49
DOIs
StatePublished - Dec 6 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Cell death inhibiting RNA (CDIR) derived from a 3′-untranslated region binds AUF1 and heat shock protein 27'. Together they form a unique fingerprint.

Cite this