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Molecular and Cellular Biology, March 2002, p. 1664-1673, Vol. 22, No. 6
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.6.1664-1673.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

RNA Destabilization by the Granulocyte Colony-Stimulating Factor Stem-Loop Destabilizing Element Involves a Single Stem-Loop That Promotes Deadenylation

R. A. Putland, T. A. Sassinis,^, J. S. Harvey,^, P. Diamond, L. S. Coles, C. Y. Brown,^, and G. J. Goodall^*

Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia 5000, Australia

Received 21 September 2001/ Returned for modification 10 October 2001/ Accepted 10 December 2001

Granulocyte colony-stimulating factor (G-CSF) mRNA contains two distinct types of cis-acting mRNA destabilizing elements in the 3'-untranslated region. In addition to several copies of the AU-rich element the G-CSF mRNA also contains a destabilizing region that includes several predicted stem-loop structures. We report here that the destabilizing activity resides in a single stem-loop structure within this region. A consensus sequence for the active structure has been derived by site-directed mutagenesis, revealing that a three-base loop of sequence YAU and unpaired bases either side of the stem contribute to the activity. The helical nature of the stem is essential and the stem must be less than 11 bp in length, but the destabilizing activity is relatively insensitive to the sequence within the helix. The stem-loop increases the rate of mRNA deadenylation, most likely by enhancing the processivity of the deadenylation reaction. A protein that binds the stem-loop, but not an inactive mutant form, has been detected in cytoplasmic lysates.

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* Corresponding author. Mailing address: Hanson Centre for Cancer Research, IMVS, Frome Rd., Adelaide, SA 5000, Australia. Phone: 61 8 8222 3430. Fax: 61 8 8232 4092. E-mail: greg.goodall{at}imvs.sa.gov.au.

Present address: Flinders University, Bedford Park, SA 5042, Australia

Present address: CSIRO Plant Industry, Hartley Grove, Urrbrae, SA 5041, Australia.

Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024.

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Molecular and Cellular Biology, March 2002, p. 1664-1673, Vol. 22, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.6.1664-1673.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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