Chromatin regulation through RNA demethylation in environmental stress response
About This Grant
Project Summary/Abstract N6-methyladenosine (m6A) is the most abundant messenger RNA (mRNA) modification and also occurs on chromatin-associated RNA in mammals. m6A significantly affects messenger RNA (mRNA) processing, export, localization, translation, and stability, thus playing critical roles in a diverse range of biological processes including stress responses. We identified the first two m6A RNA demethylases, FTO and ALKBH1, in 2011 and 2013 respectively, revealing that m6A RNA methylation is reversible and can broadly affect gene expression. Our previous research also revealed upregulation of FTO in human and mouse keratinocyte cells upon exposure to arsenic. The upregulated FTO may mediate mRNA m6A demethylation and affect cellular homeostasis, DNA damage response, and tumorigenesis induced by arsenic exposure and UV irradiation. We have recently discovered an additional layer of RNA m6A methylation regulation: we identified prevalent m6A methylation of mammalian promoter-associated RNA (paRNA), enhancer RNA (eRNA), and RNA transcribed from transposable elements (repeat RNA), which we collectively termed chromatin-associated regulatory RNAs (carRNAs). We showed that these carRNA m6A modifications could be recognized by binding proteins (readers), which recruit either the nuclear degradation exosome complex to degrade the methylated RNA or histone modification proteins to alter local histone mark deposition, thereby modulating the chromatin state and downstream transcription. Our preliminary results suggest that nuclear-localized FTO in keratinocyte cells also mediates carRNA demethylation, which can induce chromatin state and transcription changes in response to arsenic stimulation. In Aim 1, we plan to identify the exact carRNA and carRNA m6A sites affected by FTO and uncover the underlying regulatory pathways that contribute to stress response and tumorigenesis in response to arsenic exposure and UVB irradiation. We have also discovered carRNA m6A demethylation by ALKBH5, which was not previously known, in mouse embryonic stem cells (mESCs). ALKBH5 undergoes SUMOylation in cells treated with reactive oxygen species (ROS), which inhibits its demethylation activity and protects cells from DNA damage. In Aim 2, we plan to establish carRNA m6A demethylation by ALKBH5 and elucidate the underlying chromatin regulation pathways and mechanisms using mESCs as the mode system. We will also investigate how ROS-induced ALKBH5 SUMOylation may affect the chromatin state and DNA damage response in mESCs and keratinocyte cells under H2O2 treatment or arsenic exposure. Collectively, the proposed studies will determine the epitranscriptomic-epigenetic interactions in environmental stress responses and tumorigenesis for the first time. New mechanistic insights and new molecular targets for improving human health may emerge.
Grant Summary
Chromatin regulation through RNA demethylation in environmental stress response is a NIEHS - National Institute of Environmental Health Sciences grant providing up to $736K for university, nonprofit, healthcare org. Applications are due 2031-06-30 (open). Check eligibility and apply with FindGrants.
Not quite the right fit?
Search 9,000+ open grants, or get matches ranked for your organization — free.
Focus Areas
Eligibility
How to Apply
Up to $736K
2031-06-30
- 1Confirm your organization is eligible for Chromatin regulation through RNA demethylation in environmental stress response from NIEHS - National Institute of Environmental Health Sciences, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIEHS - National Institute of Environmental Health Sciences before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NIEHS - National Institute of Environmental Health Sciences's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Chromatin regulation through RNA demethylation in environmental stress response: Frequently Asked Questions
Who is eligible for the Chromatin regulation through RNA demethylation in environmental stress response?
Chromatin regulation through RNA demethylation in environmental stress response is offered by NIEHS - National Institute of Environmental Health Sciences and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Chromatin regulation through RNA demethylation in environmental stress response provide?
Chromatin regulation through RNA demethylation in environmental stress response provides up to $736K per award from NIEHS - National Institute of Environmental Health Sciences. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Chromatin regulation through RNA demethylation in environmental stress response deadline?
Applications for Chromatin regulation through RNA demethylation in environmental stress response are due 2031-06-30 (open). Because deadlines can change, verify the date with the funder, NIEHS - National Institute of Environmental Health Sciences, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Chromatin regulation through RNA demethylation in environmental stress response?
To apply for Chromatin regulation through RNA demethylation in environmental stress response, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIEHS - National Institute of Environmental Health Sciences.