Int J Biochem Mol Biol 2010;1(1):12-25

Original Article
RNA-cleaving properties of human apurinic/apyrimidinic endonuclease 1 (APE1)

Wan-Cheol Kim, Dustin King, Chow H. Lee

Chemistry Program, University of Northern British Columbia, 3333 University Way, Prince George, BC V2N 4Z9, Canada

Received February 11, 2010; accepted March 3, 2010; available online March 10, 2010; published August 1, 2010

Abstract: We have recently identified apurinic/apyrimidinic endonuclease 1 (APE1) as an endoribonuclease that cleaves c-myc mRNA in vitro
and regulates c-myc mRNA levels and half-life in cells.  This study was undertaken to further unravel the RNA-cleaving properties of APE1.  
Here, we show that APE1 cleaves RNA in the absence of divalent metal ions and, at 2 mM, Zn2+, Ni2+, Cu2+, or Co2+ inhibited the
endoribonuclease activity of APE1.  APE1 is able to cleave CD44 mRNA, microRNAs (miR-21, miR-10b), and three RNA components of SARS-
corona virus (orf1b, orf3, spike) suggesting that, when challenged, it can cleave any RNAs in vitro.  APE1 does not cleave strong double-
stranded regions of RNA and it has a strong preference for 3΄ of pyrimidine, especially towards UA, CA, and UG sites at single-stranded or
weakly paired regions.  It also cleaves RNA weakly at UC, CU, AC, and AU sites in single-stranded or weakly paired regions.  Finally, we found
that APE1 can reduce the ability of the Dicer enzyme to process pre-miRNAs in vitro.  Overall, this study has revealed some previously unknown
biochemical properties of APE1 which has implications for its role in vivo. (IJBMB1001001).

Keywords:  Endoribonuclease, APE1, CD44, miRNA, RNA structure.

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Address all correspondence to:
Chow H. Lee, PhD
Chemistry Program
University of Northern British Columbia
3333 University Way
Prince George, BC V2N 4Z9, Canada.
Tel: + 1 250 960 5413; Fax: + 1 250 960 5170
E-mail:
leec@unbc.ca
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