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Human Molecular Genetics Advance Access published online on January 18, 2008
Human Molecular Genetics, 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 Mukherjee1, Bidesh Mahata1,2, Biraj Mahato1 and Samit Adhya1,*

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

* To whom correspondence should be addressed. e-mail: sadhya{at}iicb.res.in, phone: 91 33 2473 3491; FAX: 91 33 2473 5197

Received November 27, 2007; Revised January 16, 2008; 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.

2 Present address: Department of Pharmacology, University of Wisconsin, Madison, WI 53706, U.S.A


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