Stress granules play a vital function within the stress response, arising from the aggregation of non-translating mRNAs and proteins. Though important information exists about stress granules, the mechanisms behind their mRNA localization stay partially understood. Alterations to mRNA can change the traits of the nucleobases, influencing key processes like translation, splicing, and the positioning of particular transcripts.
The researchers present 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 particularly translationally regulated.
Additionally they present that ac4C on mRNA can mediate the localization of proteins to emphasize granules. Their outcomes recommend that acetylation of mRNA regulates the localization of each stress-sensitive transcripts and RNA-binding proteins to emphasize granules and provides to our understanding of the molecular mechanisms accountable for stress granule formation.
Stress Granule Formation and RNA Modifications
Stress granules are membrane-less assemblies of mRNA-protein complexes that come up from mRNAs caught in translation initiation. RNA-protein complexes are vital for his or her formation and the mechanisms selling stress granule formation contain each standard RNA-protein interactions and interactions that embody intrinsically disordered areas of proteins.
Determine reveals stress granule formation after oxidative stress in wild-type cells and cells depleted for the ac4C acetyltransferase enzyme NAT10. Credit score: Pavel Kudrin
Stress granules have been extensively studied, and it’s well-established that they kind when translation initiation is restricted quite a lot of roles for stress granules throughout the cell have been proposed. Whereas stress granule meeting and disassembly could be regulated by varied post-translational modifications the affect of RNA modifications on their formation, dispersal, and performance stays largely unclear.
Influence of ac4C on Stress Granules and Mobile Stress Response
The RNA modification N4-acetylcytidine (ac4C) has not too long ago been proven to be deposited on mRNA and regulate translation effectivity. ac4C is conserved by means of all kingdoms of life and is induced upon a number of completely different stresses. ac4C is much less plentiful than different RNA modifications on mRNA and attributable to difficulties in exact and quantitative mapping its operate and incidence on mRNA have remained controversial.
The researchers present of their publication that ac4C is enriched in stress granules and that acetylated transcripts are predominantly localized to emphasize granules in response to oxidative stress, proposing a mannequin the place acetylation of RNA can have an effect on mRNA localization to emphasize granules, partially by affecting the translational launch of mRNA from the ribosome, offering new perception into each the operate and penalties of mRNA acetylation and mechanism of RNA localization to emphasize granules.
The findings will promote the understanding of how the cells react to emphasize and which function RNA modifications play within the course of. Each stress and RNA acetylation have implications in illness and their findings may assist make clear related molecular pathways that might be focused in illness.
Reference: “N4-acetylcytidine (ac4C) promotes mRNA localization to emphasize granules” by Pavel Kudrin, Ankita Singh, David Meierhofer, Anna Kuśnierczyk and Ulf Andersson Vang Ørom, 27 February 2024, EMBO Reviews.
DOI: 10.1038/s44319-024-00098-6
The challenge was led by Ulf A.V. Ørom’s lab at Aarhus College in Denmark, and the research concerned collaboration with researchers from the College of Tartu, Norwegian Technical College, and the Max Planck Institute for Molecular Genetics in Berlin.