# Functional RNA Modifications, Micronutrient Exposure, Developmental Disabilities

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2022 · $386,605

## Abstract

TITLE: FUNCTIONAL RNA MODIFICATIONS, MICRONUTRIENT EXPOSURE, DEVELOPMENTAL
DISABILITIES
PROJECT SUMMARY
 This proposal will combine the strengths of experimental mouse model with human prospective birth cohort
study and transdisciplinary expertise to test novel hypotheses that functional RNA methylation (coupled with
DNA methylation) may be one of the mechanisms underlying the association between maternal folate status and
child risk of autism spectrum disorders (ASD). The role of maternal folate status in child risk of ASD has received
great attention and is in debate. While many studies suggest beneficial effect of higher maternal folate intake
against autism, a few studies raised concern about the potential harm of high prenatal folate intake. In the Boston
Birth Cohort (BBC), PI's group demonstrated a wide variation of maternal folate levels, ranging from insufficiency
to excess, which is consistent with the finding in NHANES, a U.S. nationally representative sample. A `U shaped'
relationship was found between frequency of maternal multivitamin supplementation and ASD risk; this
association was further supported by the findings based on measured maternal plasma folate levels.
Furthermore, the preliminary data from PI's group suggest that maternal folate intake may have an impact on
RNA methylation metabolism. Two specific aims were proposed: Aim1 will determine folate-associated
alterations in RNA methylation and RNA/DNA methylation dynamics using mouse neural stem cells (NSCs).
RNA/DNA methylation profiles will be determined using transcriptome-wide and genome-wide bisulfite
sequencing, protein translation will be determined using polysome profiling, and folate-associated alterations in
NSC proliferation and differentiation will be characterized. In-utero folate exposure-associated RNA/DNA
methylation alterations will be determined using a mouse model. Aim 2 will determine RNA methylation sites
associated with in-utero folate exposure in cord blood samples. The inter-relationship of prenatal folate status,
RNA/DNA methylation, and child risk of ASD will be determined via the integration of individual clinical features
with corresponding RNA methylation and DNA methylation information. This proposed study, if successful, will
provide new insight on how environmental exposures (here folate is used as an example) are involved in the
functional activities of RNA modifications and RNA/DNA methylation dynamics, which in turn, may be associated
with adverse health outcomes (here ASD is used as an example). The methodologies developed will be helpful
to investigate molecular underpinnings of other micronutrients or toxicants on other health outcomes.

## Key facts

- **NIH application ID:** 10414928
- **Project number:** 5R01ES031521-03
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** XIAOBIN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,605
- **Award type:** 5
- **Project period:** 2020-08-06 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414928

## Citation

> US National Institutes of Health, RePORTER application 10414928, Functional RNA Modifications, Micronutrient Exposure, Developmental Disabilities (5R01ES031521-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414928. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*