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Research Paper

MicroRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis

Betsy T. Kren, Phillip Y.-P. Wong, Aaron Sarver, Xiaoxiao Zhang, Yan Zeng and Clifford J. Steer

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MicroRNAs (miRNAs) are a class of small ~22 nt noncoding (nc) RNAs that regulate gene expression post-transcriptionally by direct binding to target sites on mRNAs.  They comprise more than 1,000 novel species in mammalian cells and exert their function by modulating gene expression through several different mechanisms, including translational inhibition, and/or degradation of target mRNAs.  Mitochondria maintain and express their own genome, which is distinct from the nuclear transcriptional and translational apparatus.  Thus, they provide a potential site for miRNA mediated post-transcriptional regulation.  To determine whether they maintain a unique miRNA population, we examined the miRNA profile from highly purified and RNase treated mitochondria from adult rat liver.  Fifteen miRNAs were identified by microarray analysis of which, five were confirmed by TaqMan^® 5’nuclease assays using rat specific probes.  Functional analysis of the miRNAs indicated that they were not targeted to the mitochondrial genome nor were they complementary to nuclear RNAs encoding mitochondrial proteins.  Rather, the mitochondria-associated miRNAs appear to be involved in the expression of genes associated with apoptosis, cell proliferation, and differentiation.  Given the central role that mitochondria play in apoptosis, the results suggest that they may serve as reservoirs of select miRNAs that may modulate these processes in a coordinate fashion.

Authors

Betsy T. Kren Corresponding author: krenx001@umn.edu

Department of Medicine; University of Minnesota Medical School; Minneapolis, Minnesota USA

Phillip Y.-P. Wong

Department of Medicine; University of Minnesota Medical School; Minneapolis, Minnesota USA

Aaron Sarver

University of Minnesota Cancer Center; Minneapolis, Minnesota 55455 USA

Xiaoxiao Zhang

University of Minnesota Medical School Department of Pharmacology; Minneapolis, Minnesota 55455 USA

Yan Zeng

University of Minnesota Medical School Department of Pharmacology; Minneapolis, Minnesota 55455 USA

Clifford J. Steer Corresponding author: steer001@umn.edu

University of Minnesota Medical School; Department of Medicine; GI Division; Minneapolis, Minnesota 55455 USA

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