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Human Molecular Genetics Advance Access originally published online on January 18, 2008
Human Molecular Genetics 2008 17(9):1292-1298; doi:10.1093/hmg/ddn017
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Targeted mRNA degradation by complex-mediated delivery of antisense RNAs to intracellular human mitochondria

Saikat Mukherjee, Bidesh Mahata{dagger}, Biraj Mahato and Samit Adhya*

Genetic Engineering Laboratory, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700032, India

* To whom correspondence should be addressed. Tel: +91 3324733491; Fax: +91 3324735197; Email: sadhya{at}iicb.res.in

Received November 27, 2007; Accepted January 16, 2008

Mitochondrial dysfunction underlies a large number of acute or progressive diseases, as well as aging. However, proposed therapies for mitochondrial mutations suffer from poor transformation of mitochondria with exogenous DNA, or lack of functionality of the transferred nucleic acid within the organelle. We show that a transfer RNA import complex (RIC) from the parasitic protozoon Leishmania tropica rapidly and efficiently delivered signal-tagged antisense (STAS) RNA or DNA to mitochondria of cultured human cells. STAS-induced specific degradation of the targeted mitochondrial mRNA, with downstream effects on respiration. These results reveal the existence of a novel small RNA-mediated mRNA degradation pathway in mammalian mitochondria, and suggest that RIC-mediated delivery could be used to target therapeutic RNAs to the organelle within intact cells.

{dagger} Present address: Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA.


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