Intercompartment RNA Trafficking in Mitochondrial Function and Communication

Abstract

Mitochondria currently appear to be a major destination for the RNA trafficking and localization processes that control and coordinate gene expression in living cells. A large set of messenger RNAs derived from the nuclear genome is translated at the mitochondrial surface, while an increasing series of noncoding RNAs has been reported to localize in the organelles, including microRNAs, additional small noncoding RNAs, transfer RNAs, and long noncoding RNAs. These RNA species contribute to mitochondrial functions and control of organellar gene expression, but mitochondria might also store and release noncoding RNAs of nuclear origin having cytosolic targets. Conversely, data have emerged implying that small and long noncoding regulatory RNAs are generated within the organelles from the mitochondrial genome. Some of them nevertheless appeared to localize to the nucleus or were recovered in body fluids. Integrating all reported data leads to an intricate picture of multidirectional RNA trafficking and intercompartment communication that can be related to cellular homeostasis, cell differentiation, pathogenesis, or disease. However, a number of facets in this amazing picture are still a matter of debate, as the mechanisms underlying nucleic acid translocation through the mitochondrial membranes remain difficult to assess and the widespread presence of mitochondrial DNA pseudo-sequences in the nuclear genome can make the origin of some transcripts confusing. A detailed panorama of the reported mitochondrial noncoding RNAs and of the questions raised by the data is developed here in relation to major mitochondrial processes.