Open AccessCleavage of AML1/MTG8 by asymmetric hammerhead ribozymes
Author(s) -
Szyrach Mara,
Münchberg Frank E.,
Riehle Heidemarie,
Nordheim Alfred,
Krauter Jürgen,
Nagel Stefan,
Heil Gerhard,
Heidenreich Olaf
Publication year - 2001
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2001.02259.x
Subject(s) - ribozyme , biology , hammerhead ribozyme , microbiology and biotechnology , rna , mammalian cpeb3 ribozyme , ligase ribozyme , gene , genetics
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.