1. The mRNA-capping enzyme localizes to stress granules in the cytoplasm and maintains cap homeostasis of target mRNAs.
- Author
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Gayen A, Mukherjee A, Kumar K, Majumder S, Chakrabarti S, and Mukherjee C
- Subjects
- Humans, RNA Caps metabolism, Arsenites pharmacology, Oxidative Stress, Active Transport, Cell Nucleus, RNA Nucleotidyltransferases metabolism, RNA Nucleotidyltransferases genetics, Sodium Compounds pharmacology, Exportin 1 Protein, Karyopherins metabolism, Karyopherins genetics, Receptors, Cytoplasmic and Nuclear metabolism, Receptors, Cytoplasmic and Nuclear genetics, Cytoplasmic Granules metabolism, RNA Stability, Cell Nucleus metabolism, Cell Line, Tumor, Nucleotidyltransferases, RNA, Messenger metabolism, RNA, Messenger genetics, Stress Granules metabolism, Homeostasis, Cytoplasm metabolism
- Abstract
The model of RNA stability has undergone a transformative shift with the revelation of a cytoplasmic capping activity that means a subset of transcripts are recapped autonomously of their nuclear counterparts. The present study demonstrates nucleo-cytoplasmic shuttling of the mRNA-capping enzyme (CE, also known as RNA guanylyltransferase and 5'-phosphatase; RNGTT), traditionally acknowledged for its nuclear localization and functions, elucidating its contribution to cytoplasmic capping activities. A unique nuclear export sequence in CE mediates XPO1-dependent nuclear export of CE. Notably, during sodium arsenite-induced oxidative stress, cytoplasmic CE (cCE) congregates within stress granules (SGs). Through an integrated approach involving molecular docking and subsequent co-immunoprecipitation, we identify eIF3b, a constituent of SGs, as an interactive associate of CE, implying that it has a potential role in guiding cCE to SGs. We measured the cap status of specific mRNA transcripts from U2OS cells that were non-stressed, stressed and recovered from stress, which indicated that cCE-target transcripts lost their caps during stress but remarkably regained cap stability during the recovery phase. This comprehensive study thus uncovers a novel facet of cytoplasmic CE, which facilitates cellular recovery from stress by maintaining cap homeostasis of target mRNAs., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)
- Published
- 2024
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