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Molecular and Cellular Biology, February 2008, p. 939-948, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.01727-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transcript-Specific Decapping and Regulated Stability by the Human Dcp2 Decapping Protein{triangledown} ,{dagger}

You Li, Man-Gen Song, and Megerditch Kiledjian*

Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, New Jersey 08854-8082

Received 20 September 2007/ Returned for modification 22 October 2007/ Accepted 7 November 2007

mRNA decapping is a critical step in the control of mRNA stability and gene expression and is carried out by the Dcp2 decapping enzyme. Dcp2 is an RNA binding protein that must bind RNA in order to recognize the cap for hydrolysis. We demonstrate that human Dcp2 (hDcp2) preferentially binds to a subset of mRNAs and identify sequences at the 5' terminus of the mRNA encoding Rrp41, a core subunit component of the RNA exosome, as a specific hDcp2 substrate. A 60-nucleotide element at the 5' end of Rrp41 mRNA was identified and shown to confer more efficient decapping on a heterologous RNA both in vitro and upon transfection into cells. Moreover, reduction of hDcp2 protein levels in cells resulted in a selective stabilization of the Rrp41 mRNA, confirming it as a downstream target of hDcp2 regulation. These findings demonstrate that hDcp2 can specifically bind to and regulate the stability of a subset of mRNAs, and its intriguing regulation of the 3'-to-5' exonuclease exosome subunit suggests a potential interplay between 5'-end mRNA decapping and 3'-end mRNA decay.

* Corresponding author. Mailing address: Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082. Phone: (732) 445-0796. Fax: (732) 445-0104. E-mail: kiledjian{at}biology.rutgers.edu

{triangledown} Published ahead of print on 26 November 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, February 2008, p. 939-948, Vol. 28, No. 3
0270-7306/08/$08.00+0     doi:10.1128/MCB.01727-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jiao, X., Chen, H., Chen, J., Herrup, K., Firestein, B. L., Kiledjian, M. (2009). Modulation of Neuritogenesis by a Protein Implicated in X-Linked Mental Retardation. J. Neurosci. 29: 12419-12427 [Abstract] [Full Text]  
  • Li, Y., Ho, E. S., Gunderson, S. I., Kiledjian, M. (2009). Mutational analysis of a Dcp2-binding element reveals general enhancement of decapping by 5'-end stem-loop structures. Nucleic Acids Res 37: 2227-2237 [Abstract] [Full Text]  
  • Oshikawa, M., Sugai, Y., Usami, R., Ohtoko, K., Toyama, S., Kato, S. (2008). Fine Expression Profiling of Full-length Transcripts using a Size-unbiased cDNA Library Prepared with the Vector-capping Method. DNA Res 15: 123-136 [Abstract] [Full Text]  


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