The identification of mecciRNAs and their roles in mitochondrial entry of proteins

Abstract

Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by nuclear genome have to be imported from the cytosol into the mitochondria. Here we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components of mitochondrial protein and RNA importation such as TOM40 and PNPASE interact with mecciRNAs and regulate protein entry. Expression of mecciRNAs is regulated, and these transcripts are critical for mitochondria in adapting to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to eukaryotic circular RNAs, and shed novel lights on communication between mitochondria and nucleus.

Circular RNAs in renal cell carcinoma: implications for tumorigenesis, diagnosis, and therapy

“…However, some studies have also shown that EIciRNAs and ciRNAs can enhance the transcription and splicing of their parental genes by interacting with RNA polymerase II (pol II) or the essential splicing factor U1 small nuclear ribonucleoprotein (snRNP) [61,62]. Hundreds of circRNAs, encoded by the mitochondrial genome (mecciRNA) in both human and mouse cells, were recently identified [63]. The study found that some mec-ciRNAs can act as molecular chaperones to facilitate mitochondrial transport of proteins encoded by nuclear genes, which is essential for mitochondrial adaptation to physiological conditions.…”

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“…F-circrna is synthesized from the transcribed exons of several nuclear genes as a result of chromosomal translocation (36). lastly, meccirna is produced from mitochondrial genes (37). ecircrnas are the most common type of circrna.…”

Epigenetic Regulation by Non-Coding RNAs in the Avian Immune System

“…So circRNAs are mainly classified in exonic circular RNA (eciRNA), intronic circular RNA (ciRNA), and exon-intron circular RNA (EIciRNA). But recently, circRNAs from mitochondria DNA were newly investigated, this kind of circRNA was called mecciRNAs [ 26 ]. Because circRNAs have no free 5′cap and 3′ poly A tail, it makes them not easily degraded by RNase.…”