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Inhibition of translation by RNA–small molecule interactions

Published online by Cambridge University Press:  24 April 2002

ISABELLE HARVEY ,
PHILIPPE GARNEAU  and
JERRY PELLETIER
ISABELLE HARVEY
Affiliation:
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada
PHILIPPE GARNEAU
Affiliation:
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada
JERRY PELLETIER
Affiliation:
Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada McGill Cancer Center, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, H3G 1Y6, Canada
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Abstract

Small molecule ligand–RNA interactions have the potential to influence gene expression at a variety of steps and in a number of ways. Here, we demonstrate that such interactions are sufficiently stable to inhibit translation of eukaryotic mRNAs in vitro and in vivo. Inhibition is only observed when the 5′ UTR of the mRNA is targeted, and the response is proportional to the number of binding sites within this region. We find that small molecule ligand–RNA interactions can be sufficiently stable to prevent 80S ribosome assembly on an mRNA template. The ability to specifically ablate expression of a defined mRNA with a small molecule ligand demonstrates proof of principle for pharmacological targeting aimed at controlling translation of specific mRNAs.

Keywords

gene regulationmolecular switchsmall molecule ligandtranslation
Type
Research Article
Information
RNA , Volume 8 , Issue 4 , April 2002 , pp. 452 - 463
Copyright
2002 RNA Society

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