# Transcription arrest induces formation of RNA granules in mitochondria

## TL;DR

This study shows that when mitochondrial transcription is stopped, RNA granules form to protect RNA and help cells recover.

## Contribution

The discovery of inhibition granules in mitochondria as a response to transcription arrest is novel.

## Key findings

- Transcription inhibition leads to formation of RNA granules in mitochondria.
- Inhibition granules stabilize certain mitochondrial mRNAs during transcription arrest.
- Cells recover by resolving granules and restarting transcription.

## Abstract

In this study, the spatial distribution of mitochondrial-encoded RNAs is investigated and shows that upon transcription arrest, RNAs form granules that show protectivity for transcripts.

Mitochondrial gene expression regulation is required for the biogenesis of oxidative phosphorylation (OXPHOS) complexes, yet the spatial organization of mitochondrial RNAs (mt-RNAs) remains unknown. Here, we investigated the spatial distribution of mt-RNAs during various cellular stresses using single-molecule RNA-FISH. We discovered that transcription inhibition leads to the formation of distinct RNA granules within mitochondria, which we term inhibition granules. These structures differ from canonical mitochondrial RNA granules and form in response to multiple transcription arrest conditions, including ethidium bromide treatment, specific inhibition or stalling of the mitochondrial RNA polymerase, and depletion of the SUV3 helicase. Inhibition granules appear to stabilize certain mt-mRNAs during prolonged transcription inhibition. This phenomenon coincides with an imbalance in OXPHOS complex expression, where mitochondrial-encoded transcripts decrease while nuclear-encoded subunits remain stable. We found that cells recover from transcription inhibition via resolving the granules, restarting transcription, and repopulating the mitochondrial network with mt-mRNAs within hours. We suggest that inhibition granules may act as a reservoir to help overcome OXPHOS imbalance during recovery from transcription arrest.