RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in Caenorhabditis elegans

Chonglin Yang, Nieng Yan, Jay Parish, Xiaochen Wang, Yigong Shi, Ding Xue

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Bcl-2 family proteins include anti- and proapoptotic factors that play important roles in regulating apoptosis in diverse species. Identification of compounds that can modulate the activities of Bcl-2 family proteins will facilitate development of drugs for treatment of apoptosis-related human diseases. We used an in vitro selection method named systematic evolution of ligands by exponential enrichment (SELEX) to isolate RNA aptamers that bind the Caenorhabditis elegans Bcl-2 homolog CED-9 with high affinity and specificity and tested whether these aptamers modulate programmed cell death in C. elegans. Five CED-9 aptamers were isolated and classified into three groups based on their predicted secondary structures. Biochemical analyses indicated that two of these aptamers, R9-2 and R9-7, and EGL-1, an endogenous CED-9-binding proapoptotic protein, bound to distinct regions of CED-9. However, these two aptamers shared overlapping CED-9 binding sites with CED-4, another CED-9-binding proapoptotic factor. Importantly ectopic expression of these two aptamers in touch receptor neurons induced efficient killing of these neurons largely in a CED-3 caspase-dependent manner. These findings suggest that RNA aptamers can be used to modulate programmed cell death in vivo and can potentially be used to develop drugs to treat human diseases caused by abnormal apoptosis.

Original languageEnglish (US)
Pages (from-to)9137-9144
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number14
DOIs
StatePublished - Apr 7 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in Caenorhabditis elegans'. Together they form a unique fingerprint.

Cite this