A Recent Finding Shows How Cells Protect Themselves Under Tense Circumstances

Stress granules, which are produced when non-translating mRNAs and proteins aggregate, are essential to the stress response. Stress granules are well established, although the mechanisms behind their mRNA localization are still not fully understood. Changes to mRNA can affect important functions like translation, splicing, and the location of particular transcripts by altering the properties of the nucleobases.

The researchers demonstrate that transcripts abundant in stress granules are associated with the RNA modification N4-acetylcytidine (ac4C) on mRNA and that transcripts localized with ac4C in stress granules are particularly translationally controlled.

Additionally, they demonstrate how ac4C on mRNA might control protein localization to stress granules. Their findings contribute to our knowledge of the molecular processes underlying stress granule formation by indicating that acetylation of mRNA controls the location of RNA-binding proteins and stress-sensitive transcripts to stress granules.

Formation of Stress Granules and Modifications to RNA

Stress granules are mRNA-protein complexes assembled without a membrane that result from mRNAs that become trapped during translation initiation. The production of stress granules is dependent on RNA-protein complexes, and the processes that foster their creation involve both traditional RNA-protein interactions and interactions involving intrinsically disordered protein regions.

Numerous functions for stress granules within the cell have been suggested, and it is well known from considerable research that they arise when translation initiation is restricted. Although several post-translational modifications can control the assembly and disassembly of stress granules, it is yet unclear how RNA alterations affect the creation, distribution, and function of these structures.

Effect of ac4C on Stress Granules and Cellular Stress Response

It has recently been demonstrated that the RNA modification N4-acetylcytidine (ac4C) is deposited on mRNA and controls translation efficiency. All kingdoms of life have conserved ac4C, which is induced by a variety of stressors. ac4C is less common than other RNA modifications on mRNA, and because it is challenging to map its function and occurrence on mRNA precisely and quantitatively, the topic has remained debatable.

In their publication, the researchers demonstrate that ac4C is enriched in stress granules and that, in response to oxidative stress, acetylated transcripts are primarily localized to stress granules. They also propose a model in which mRNA acetylation can influence mRNA localization to stress granules, partly through influencing the translational release of mRNA from the ribosome. This model offers new insights into the role and effects of mRNA acetylation as well as the mechanism underlying RNA localization to stress granules.

The results will advance our knowledge of how cells respond to stress and the part RNA changes play in that response. Their research may assist clarify pertinent biological pathways that may be targeted in disease. Stress and RNA acetylation both have significance in disease.