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

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.

Molluscan mitochondrial genomes break the rules

“…More recently, Passamonti et al . [173] reported in vivo clues of the activity of two sncRNAs in R. philippinarum . Small mitochondrial RNAs have also been predicted in silico in several species of amniotes [174], and in Drosophila melanogaster , Danio rerio and Mus musculus [173].…”

Unraveling mitochondrial piRNAs in mouse embryonic gonadal cells

“…The biogenesis processes of piRNAs have been established in various animal species, with elements common to most of them, in both germ and somatic cells 26 – 29 . The association of piRNAs with mitochondria has been well documented 30 – 32 . Moreover, the presence of piRNAs within the mitochondria has been detected 33 , although their biogenesis, variability, and potential functionality is still unclear.…”

The Mitochondrial Genome of a Freshwater Pelagic Amphipod Macrohectopus branickii Is among the Longest in Metazoa

“…The mt genomes of many organisms contain open reading frames (ORFs) with unknown origins and functions (referred to as mtORFans) but experimentally proven expression [ 36 ]. Such sequences have been found in corals from the family Pocilloporidae ( tmp362 ) [ 37 ], sea anemones Anemonia viridis and Anemonia majano ( orfA ) [ 38 ], insects of gen. Campsomeris (Scoliidae) ( qnu ) [ 39 ], Bivalvia mollusks (F- and M-orf) [ 40 ], etc., and assumed to be regular PCGs [ 37 , 39 ] or pseudogenes affecting the expression of nuclear genes [ 41 , 42 , 43 ].…”