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Cleavage of AML1/MTG8 by asymmetric hammerhead ribozymes

Lookup NU author(s): Professor Olaf Heidenreich

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Abstract

The chromosomal translocation t(8;21) is one of the most frequent aberrations associated with acute myeloid leukaemia. It joins the 5' section of the AML1 gene with the almost complete open reading frame of MTG8 (ETO). The resulting fusion RNA represents a leukaemia-specific target for antisense/ribozyme inhibition. We tested several asymmetric hammerhead ribozymes targeted against the fusion site for their ability to cleave the AML1/MTG8 RNA at low magnesium concentrations. One ribozyme cleaves AML1/MTG8 RNA with high catalytic efficiency without binding or cleaving the wild-type AML1 transcript. The presence of cellular RNA does not affect the cleavage. Injection of AML1/MTG8 RNA and ribozyme RNA into Xenopus eggs or oocytes causes a specific reduction of AML1/MTG8 protein expression. Asymmetric anti-AML1/MTG8 ribozymes may be valuable modulators of AML1/MTG8 expression in leukaemic cells.

Publication metadata

Author(s): Szyrach M, Munchberg FE, Riehle H, Nordheim A, Krauter J, Nagel S, Heil G, Heidenreich O

Publication type: Article

Publication status: Published

Journal: European Journal of Biochemistry

Year: 2001

Volume: 268

Issue: 12

Pages: 3550-3557

ISSN (print): 1742-464X

ISSN (electronic): 1742-4658

URL: http://dx.doi.org/10.1046/j.1432-1327.2001

DOI: 10.1046/j.1432-1327.2001.02259.x

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