Clues of in vivo nuclear gene regulation by mitochondrial short non-coding RNAs

Marco Passamonti,Federico Plazzi,Manuel Delpero,Marco Calderone

doi:10.1038/s41598-020-65084-z

Marco Passamonti, Federico Plazzi + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-65084-z

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Abstract

Gene expression involves multiple processes, from transcription to translation to the mature, functional peptide, and it is regulated at multiple levels. Small RNA molecules are known to bind RNA messengers affecting their fate in the cytoplasm (a process generically termed ‘RNA interference’). Such small regulatory RNAs are well-known to be originated from the nuclear genome, while the role of mitochondrial genome in RNA interference was largely overlooked. However, evidence is growing that mitochondrial DNA does provide the cell a source of interfering RNAs. Small mitochondrial highly transcribed RNAs (smithRNAs) have been proposed to be transcribed from the mitochondrion and predicted to regulate nuclear genes. Here, for the first time, we show in vivo clues of the activity of two smithRNAs in the Manila clam, Ruditapes philippinarum. Moreover, we show that smithRNAs are present and can be annotated in representatives of the three main bilaterian lineages; in some cases, they were already described and assigned to a small RNA category (e.g., piRNAs) given their biogenesis, while in other cases their biogenesis remains unclear. If mitochondria may affect nuclear gene expression through RNA interference, this opens a plethora of new possibilities for them to interact with the nucleus and makes metazoan mitochondrial DNA a much more complex genome than previously thought.

Highlights

Gene expression involves multiple processes, from transcription to translation to the mature, functional peptide, and it is regulated at multiple levels
In the human Mitochondrial DNA (mtDNA), a total of 31 short non-coding RNA transcripts (sncRNAs) mapping to 17 loci were originally annotated[36]. These loci prevalently code for tRNA-encoding genes (tRNAs), and it is known that tRNAs may be processed by Dicer and other RNAses in the cytoplasm into a wide array of small RNA molecules that enter RNA-silencing pathways[37,38]
We focused on gathering clues of functionality of these sncRNAs in regulating nuclear genes

Summary

Introduction

Gene expression involves multiple processes, from transcription to translation to the mature, functional peptide, and it is regulated at multiple levels. In the human mtDNA, a total of 31 sncRNAs mapping to 17 loci (prevalently tRNAs) were originally annotated[36] These loci prevalently code for tRNAs, and it is known that tRNAs may be processed by Dicer and other RNAses in the cytoplasm into a wide array of small RNA molecules that enter RNA-silencing pathways[37,38]. Mitochondrial genome-encoded small RNAs (mitosRNAs39) are known from different species[39,40,41]; involved in many physiological processes, like anoxic response[41] or gametogenesis[40], mitosRNAs www.nature.com/scientificreports were never directly associated to nuclear target mRNAs. the possible involvement of mitochondrial non-coding RNAs in nuclear regulation is an expanding research field[42,43]

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