Work

Editor's evaluation: Regulation of nuclear transcription by mitochondrial RNA in endothelial cells

Year: 2023

Type: peer-review

Abstract: Chromatin-associated RNAs (caRNAs) form a relatively poorly recognized layer of the epigenome.The caRNAs reported to date are transcribed from the nuclear genome.Here, leveraging a recently developed assay for detection of caRNAs and their genomic association, we report that mitochondrial RNAs (mtRNAs) are attached to the nuclear genome and constitute a subset of caRNA, thus termed mt-caRNA.In four human cell types analyzed, mt-caRNAs preferentially attach to promoter regions.In human endothelial cells (ECs), the level of mt-caRNA-promoter attachment changes in response to environmental stress that mimics diabetes.Suppression of a non-coding mt-caRNA in ECs attenuates stress-induced nascent RNA transcription from the nuclear genome, including that of critical genes regulating cell adhesion, and abolishes stress-induced monocyte adhesion, a hallmark of dysfunctional ECs.Finally, we report increased nuclear localization of multiple mtRNAs in the ECs of human diabetic donors, suggesting many mtRNA translocate to the nucleus in a cell stress and disease-dependent manner.These data nominate mt-caRNAs as messenger molecules responsible for mitochondrial-nuclear communication and connect the immediate product of mitochondrial transcription with the transcriptional regulation of the nuclear genome. Editor's evaluationThis work is fundamental in providing compelling evidence of mitochondria-encoded RNAs playing a role in controlling nuclear gene expression.How mitochondria and the nucleus communicate is an important yet, not well-appreciated area of biology.Using the iMARGI (in situ mapping of RNA-Genome Interactions) technology developed by this team, the authors found that mitochondriaencoded RNAs play an unexpected role in regulating nuclear gene expressions in endothelial cells and intriguingly, depletion or overexpression of a specific mt-caRNA altered stress-induced transcription of nuclear genes encoding for innate inflammation and endothelial activation.Overall, these findings are interesting and supported by experimental confirmation, bulk-RNA-seq, and

Source: eLife

DOI: 10.7554/elife.86204.sa0

Author: Detlef Weigel

Institution: Max Planck Institute for Biology

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500