Stress granules play a crucial role in the stress response, arising from the aggregation of non-translating mRNAs and proteins. Although significant knowledge exists about stress granules, the mechanisms behind their mRNA localization remain partially understood. Alterations to mRNA can change the characteristics of the nucleobases, influencing key processes like translation, splicing, and the positioning of specific transcripts.
The researchers show that the RNA modification N4-acetylcytidine (ac4C) on mRNA associates with transcripts enriched in stress granules and that stress granule localized transcripts with ac4C are specifically translationally regulated.
They also show that ac4C on mRNA can mediate the localization of proteins to stress granules. Their results suggest that acetylation of mRNA regulates the localization of both stress-sensitive transcripts and RNA-binding proteins to stress granules and adds to our understanding of the molecular mechanisms responsible for stress granule formation.
Stress Granule Formation and RNA Modifications
Stress granules are membrane-less assemblies of mRNA-protein complexes that arise from mRNAs stuck in translation initiation. RNA-protein complexes are important for their formation and the mechanisms promoting stress granule formation involve both conventional RNA-protein interactions and interactions that encompass intrinsically disordered regions of proteins.
Figure shows stress granule formation after oxidative stress in wild-type cells and cells depleted for the ac4C acetyltransferase enzyme NAT10. Credit: Pavel Kudrin
Stress granules have been extensively studied, and it is well-established that they form when translation initiation is limited a variety of roles for stress granules within the cell have been proposed. While stress granule assembly and disassembly can be regulated by various post-translational modifications the impact of RNA modifications on their formation, dispersal, and function remains largely unclear.
Impact of ac4C on Stress Granules and Cellular Stress Response
The RNA modification N4-acetylcytidine (ac4C) has recently been shown to be deposited on mRNA and regulate translation efficiency. ac4C is conserved through all kingdoms of life and is induced upon several different stresses. ac4C is less abundant than other RNA modifications on mRNA and due to difficulties in precise and quantitative mapping its function and occurrence on mRNA have remained controversial.
The researchers show in their publication that ac4C is enriched in stress granules and that acetylated transcripts are predominantly localized to stress granules in response to oxidative stress, proposing a model where acetylation of RNA can affect mRNA localization to stress granules, in part by affecting the translational release of mRNA from the ribosome, providing new insight into both the function and consequences of mRNA acetylation and mechanism of RNA localization to stress granules.
The findings will promote the understanding of how the cells react to stress and which role RNA modifications play in the process. Both stress and RNA acetylation have implications in disease and their findings could help shed light on relevant molecular pathways that could be targeted in disease.
Reference: “N4-acetylcytidine (ac4C) promotes mRNA localization to stress granules” by Pavel Kudrin, Ankita Singh, David Meierhofer, Anna Kuśnierczyk and Ulf Andersson Vang Ørom, 27 February 2024, EMBO Reports.
DOI: 10.1038/s44319-024-00098-6
The project was led by Ulf A.V. Ørom’s lab at Aarhus University in Denmark, and the study involved collaboration with researchers from the University of Tartu, Norwegian Technical University, and the Max Planck Institute for Molecular Genetics in Berlin.

News
By working together, cells can extend their senses beyond their direct environment
The story of the princess and the pea evokes an image of a highly sensitive young royal woman so refined, she can sense a pea under a stack of mattresses. When it comes to [...]
Overworked Brain Cells May Hold the Key to Parkinson’s
Scientists at Gladstone Institutes uncovered a surprising reason why dopamine-producing neurons, crucial for smooth body movements, die in Parkinson’s disease. In mice, when these neurons were kept overactive for weeks, they began to falter, [...]
Old tires find new life: Rubber particles strengthen superhydrophobic coatings against corrosion
Development of highly robust superhydrophobic anti-corrosion coating using recycled tire rubber particles. Superhydrophobic materials offer a strategy for developing marine anti-corrosion materials due to their low solid-liquid contact area and low surface energy. However, [...]
This implant could soon allow you to read minds
Mind reading: Long a science fiction fantasy, today an increasingly concrete scientific goal. Researchers at Stanford University have succeeded in decoding internal language in real time thanks to a brain implant and artificial intelligence. [...]
A New Weapon Against Cancer: Cold Plasma Destroys Hidden Tumor Cells
Cold plasma penetrates deep into tumors and attacks cancer cells. Short-lived molecules were identified as key drivers. Scientists at the Leibniz Institute for Plasma Science and Technology (INP), working with colleagues from Greifswald University Hospital and [...]
This Common Sleep Aid May Also Protect Your Brain From Alzheimer’s
Lemborexant and similar sleep medications show potential for treating tau-related disorders, including Alzheimer’s disease. New research from Washington University School of Medicine in St. Louis shows that a commonly used sleep medication can restore normal sleep patterns and [...]
Sugar-Coated Nanoparticles Boost Cancer Drug Efficacy
A team of researchers at the University of Mississippi has discovered that coating cancer treatment carrying nanoparticles in a sugar-like material increases their treatment efficacy. They reported their findings in Advanced Healthcare Materials. Over a tenth of breast [...]
Nanoparticle-Based Vaccine Shows Promise in Fighting Cancer
In a study published in OncoImmunology, researchers from the German Cancer Research Center and Heidelberg University have created a therapeutic vaccine that mobilizes the immune system to target cancer cells. The researchers demonstrated that virus peptides combined [...]
Quantitative imaging method reveals how cells rapidly sort and transport lipids
Lipids are difficult to detect with light microscopy. Using a new chemical labeling strategy, a Dresden-based team led by André Nadler at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) and [...]
Ancient DNA reveals cause of world’s first recorded pandemic
Scientists have confirmed that the Justinian Plague, the world’s first recorded pandemic, was caused by Yersinia pestis, the same bacterium behind the Black Death. Dating back some 1,500 years and long described in historical texts but [...]
“AI Is Not Intelligent at All” – Expert Warns of Worldwide Threat to Human Dignity
Opaque AI systems risk undermining human rights and dignity. Global cooperation is needed to ensure protection. The rise of artificial intelligence (AI) has changed how people interact, but it also poses a global risk to human [...]
Nanomotors: Where Are They Now?
First introduced in 2004, nanomotors have steadily advanced from a scientific curiosity to a practical technology with wide-ranging applications. This article explores the key developments, recent innovations, and major uses of nanomotors today. A [...]
Study Finds 95% of Tested Beers Contain Toxic “Forever Chemicals”
Researchers found PFAS in 95% of tested beers, with the highest levels linked to contaminated local water sources. Per- and polyfluoroalkyl substances (PFAS), better known as forever chemicals, are gaining notoriety for their ability [...]
Long COVID Symptoms Are Closer To A Stroke Or Parkinson’s Disease Than Fatigue
When most people get sick with COVID-19 today, they think of it as a brief illness, similar to a cold. However, for a large number of people, the illness doesn't end there. The World [...]
The world’s first AI Hospital, developed in China is transforming healthcare
Artificial Intelligence and its developments have had a revolutionary impact on society, and healthcare is not an exception. China has made massive strides in AI integrated healthcare, and continues to do so as AI [...]
Scientists Rewire Immune Cells To Supercharge Cancer-Fighting Power
Blocking a single protein boosts T cell metabolism and tumor-fighting strength. The discovery could lead to next-generation cancer immunotherapies. Scientists have identified a strategy to greatly enhance the cancer-fighting abilities of the immune system’s [...]