The Epitranscriptome | National Institute of Environmental Health Sciences
Source: https://www.niehs.nih.gov/research/supported/health/epitranscriptome
Archived: 2026-04-23 17:18
The Epitranscriptome | National Institute of Environmental Health Sciences
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The Epitranscriptome
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Table of Contents
Introduction
What NIEHS Is Doing
NIEHS Supported Research
Grantees
Related Links
Introduction
Chemical modifications of protein, DNA, and RNA molecules play critical roles in regulating gene expression. Emerging evidence suggests post-transcriptional RNA modifications have major roles in multiple basic biological processes. Epitranscriptomics (also called RNA epigenetics) can be defined as all RNA modifications that exist within a cell. Just as epigenetic modifications regulate gene expression by modulating DNA accessibility, epitranscriptomic changes regulate gene expression by affecting RNA stability, localization, and processing. These chemical modifications are controlled by proteins that function as readers, writers, and erasers (RWEs). Writers and erasers can add or remove specific modifications, respectively, while readers interpret and process them. Studies in yeast, fruit flies, rodents and human models demonstrate that stressors can induce RNA modifications, with specific reprogramming of some regulatory RNAs.
What NIEHS Is Doing
Over 170 RNA base modifications have been identified. (Source: McCown PJ, Ruszkowska A, Kunkler CN, Breger K, Hulewicz JP, Wang MC, Springer NA, Brown JA. 2020. Naturally occurring modified ribonucleosides. Wiley Interdiscip Rev RNA 11(5):e1595. [
Abstract
])
The NIEHS environmental epitranscriptomics portfolio supports research focused on how environmental exposures affect the epitranscriptome and related health impacts. So far, over 170 RNA base modifications have been identified that have far-reaching impacts on molecular pathways associated with the development and progression of adverse health outcomes. Researchers are using a variety of methods, including cell cultures, animal models and population-based approaches to determine how environmental toxicants impact RNA biology and human health. Changes to the epitranscriptome are also being studied as potential biomarkers of exposure and exposure-induced pathologies.
The portfolio currently has approximately 40 active grants that examine a number of exposures including metals (As, Ni), phosphate, UVB, vinyl chloride, high fat diets (HFDs), and agents that induce reactive oxygen species (ROS). These grants cover a range of health outcomes such as transgenerational metabolic outcomes, lung and cardiovascular disease, cancers, neurodevelopmental and neurodegenerative disorders. There are currently over 100 diseases that are associated with aberrant epitranscriptomic processes. How environmental exposures could impact epitranscriptomics and related disorders is an ongoing area of research.
As our ability to sequence and analyze the epitranscriptome evolves, so too will the research that NIEHS supports. NIEHS-funded environmental epitranscriptomics research could enhance our understanding of how environmental factors influence human health and change how we diagnose and treat disease.
NIEHS Supported Research
Readers, writers, and erasers regulate RNA modifications and their roles in the cell.(Source: Uddin MB, Wang Z, Yang C. 2020. Dysregulations of Functional RNA Modifications in Cancer, Cancer Stemness and Cancer Therapeutics. Theranostics 10(7):3164-3189. [
Abstract
])
Stress and the Epitranscriptome
The ability of the epitranscriptome to respond to stress is vital for health and survival. One of the most prevalent RNA modifications, m6A, regulates mRNA stability, processing, localization, and translation efficiency depending on its location within the mRNA strand. In response to oxidative stress, the writer proteins METTL3/METTL14 deposit m6A, inducing upregulation of antioxidant genes. DNA damage resulting from UV irradiation also leads to m6A being recruited to the damaged sites and facilitating repair mechanisms. Other reader and writer proteins can also regulate protein translation and lipid metabolism in response to stress.
Exposures and Disease
Environmental exposures can cause changes in the epitranscriptome that contribute to disease pathology, such as liver disease and cancer. METTL3, METTL14, and FTO are writers that deposit m6A on RNA molecules. Overexpression occurs often in cancerous tissues and is associated with worse outcomes in cancer patients. RWEs and m6A dysregulation can be driven by toxic metal exposures such as arsenic, hexavalent chromium, and cadmium. Aberrant m6A modifications play a key role in carcinogenesis and the adverse health outcomes caused by these exposures. METTL3 and FTO have increased expression in fatty liver disease and drive increased m6A profiles in genes important for lipid metabolism. These proteins are impacted by a high fat diet and other exposures, such as vinyl chloride and polychlorinated biphenyls.
Transfer RNA (tRNA) plays a key role in protein translation and is heavily modified. These modifications affect tRNA structure, stability, and function, leading to significant effects on protein translation. Mutations in the enzymes that regulate tRNA modifications can cause multiple types of disorders such as cancer, neurological disorders, and mitochondrial diseases. Of the 75 proteins that have been found to regulate tRNA modifications, 54 have been associated with tRNA modopathies.
Epitranscriptomics and Development
METTL3 is critical during early development as m6A modifications are critical for regulating maternally deposited mRNA in early development. m6A readers and writers are involved in neurodevelopment and important for processes such as neuron differentiation, axon guidance, and astrocyte proliferation. How early exposures might impact the epitranscriptome and drive developmental defects is an ongoing area of study.
Similar to DNA methylation, RNA modifications can also be passed down from parent to offspring. Recent studies have shown that small RNAs in sperm can be passed from one generation to the next. Environmental exposures can modify sperm RNA which contribute to offspring phenotypes in a process referred to as transgenerational inheritance.
Grantees
Project Title
Principal Investigator
Institution
Grant Number
ALKBH5 and Nickel-Induced Lung Carcinogenesis
Hong Sun, Ph.D.
New York University School of Medicine
R21ES034811-02
Chemical Biology of DNA and RNA Alkylation
Yinsheng Wang, Ph.D.
University of California Riverside
R35ES031707
Decoding the Signature of Sperm RNA & RNA Modification of Environmental Stressors on the Intergenerational Transmission of Metabolic Phenotypes
Qi Chen, Ph.D.
University of Utah
R01ES032024-05
Determining the Role of RNA abasic Sites in Gene Regulation
Vivian Cheung, Ph.D.
Brown University
R21ES034919-02
Dysregulations of Functional RNA Modifications and Hexavalent Chromium Lung Carcinogenesis
Chengfeng Yang, Ph.D.
State University of New York at Stony Brook
R01ES032787-04
Epitranscriptomic Mechanism of Environmental Stress Response and Tumorigenesis
Yu-Ying He, Ph.D.
University of Chicago
R35ES031693-02
Functional Alterations of the Dihydrouridine Landscape in Response to Environmental Stress
Wendy Gilbert, Ph.D.
Yale University
R21ES031525-02
Functional RNA Modifications, Micronutrient Exposure, Developmental Disabilities
Hehuang Xie, Ph.D.
Virginia Polytechnic Institute and State University
R01ES031521-05
Heavy Metal-Stimulated Signal Transduction: New Metal-Regulatory and -Responsive Mechanisms
Matthew Ross, Ph.D.
University of Chicago
K99ES034084-01A1
Imprinted Gene Regulation by
in utero
Lead Exposure in Mice
Bambarendage Pinithi Perera, Ph.D.
University of Michigan at Ann Arbor
K01ES035064-01A1
Mechanisms of Transgenerational Epigenetic Inheritance
Victor Corces, Ph.D.
Emory University
R01ES027859-07
METTL3 in Chromium-Induced Angiogenesis and Carcinogenesis
Steven McMahon, Ph.D.
Thomas Jefferson University
R01ES033197-03
MGMT Down-Regulation in the Carcinogenicity of Hexavalent Chromium
Zhishan Wang, Ph.D
State University of New York Stony Brook
R01ES029496-05
Molecular Mechanisms Underlying Metabolic Reprogramming by Paternal Benzene Exposure
Heidi Lempradl, Ph.D.
Van Andel Research Institute
R56ES034765-01A1
Modulation of RNA Binding Proteins in Xenobiotic-Induced Hepatotoxicity
Yogesh Saini, Ph.D.
North Carolina State University
R01ES033709-02
N6-Methyladenosine (m6A) Interplays with RNA and DNA Damage to Regulate DNA Repair
Yuan Liu, M.D., Ph.D.
Florida International University
R03ES035200-02
Nitric Oxide as a Novel Regulator of Alternative Splicing
Joseph Schindler, M.D., Ph.D.
Case Western Reserve University
F30ES035247-02
Novel Epitranscriptomic Mechanisms in Metal Neurotoxicity
Anumantha Gounder Kanthasamy, Ph.D.
Iowa State University
1R01ES036241
Oxidative Stress and RNA Methylation
Ricardo Aguiar, Ph.D.
University of Texas Health Science Center
R01ES031522-05
Prenatal Traffic-Related Air Pollutants, Placental Epitranscriptomics, and Child Cognition
Julie Herbstman, Ph.D.
Columbia University Health Sciences
R01ES032818-03
Pho-m6A Assay: A Phosphoselective Method to Quantify Dynamics of m6A in mRNA
Qiuying Chen, Ph.D.
Weill Medical College of Cornell University
R21ES032347-02
RNA Modifications by Paternal Exposure to Arsenic and Intergenerational Effects on Sperm Quality
Shuk-Mei Ho, Ph.D.
University of Arkansas for Medical Sciences
R01ES032675-03
Role of m6A RNA Modifications in AHR-Mediated Developmental Toxicity
Neelakanteswar Aluru, Ph.D.
Woods Hole Oceanographic Institution
R21ES035153-01
Role of PXR in EDC-Induced Cardiovascular Disease
Changcheng Zhou, Ph.D.
University of California, Riverside
R35ES035015-02
Systems-Wide Analysis of Oxidative Stress-Responsive m6A Epitranscriptome
Yi-Lan Weng, Ph.D.
The Methodist Hospital Research Institute
R01ES031511-04
The Epitranscriptome as a Novel Mechanism of Arsenic-Induced Diabetes
Ana Navas-Acien, Ph.D.
Columbia University Health Sciences
R01ES032638-04
The Placental Epitranscriptome as a Novel Mechanism Behind Prenatal Metal Mixture Exposures and Child Growth and Development
Allison Kupsco, Ph.D.
Columbia University Health Sciences
R01ES035908-01
The Role of m6A-RNA Methylation in Memory Formation and Recall and its Modulation and Influence on Long-Term Outcomes as a Consequence of Early Life Lead Exposure
Jay Schneider, Ph.D.
Thomas Jefferson University
R01ES034077-02
Translational Regulation During Cigarette Smoking-Induced Reprogramming of the tRNA Epitranscriptome,
in vitro
and in a Mouse Smoking Model
Thomas Begley, Ph.D.
State University of New York At Albany
R01ES031529-05
Translational Regulation in Exposure Biology - Xenobiotic-Induced Reprograming of tRNA Modifications and Selective Translation of Codon-Biased Response Genes in Rat and Human Models
Thomas Begley, Ph.D.
State University of New York At Albany
R01ES026856-09
Understanding mRNA Condensation and Its Role in Translational Control During Stress
Hendrik Glauninger
University of Chicago
F30ES032665-04
Using Riboglow to Define RNP Interactions in Response to Environmental Stress
Erin Richards
University of Colorado Boulder
F31ES033919-03
Related Links
Article in Science on NASEM Report
Congressional Briefing: The Urgent Need to Advance RNA Science
Decoding RNA Mysteries: A New Era for Biology and Medicine - Futurum
Environmental Epigenomics
Epitranscriptomics Crosstalks and Toxicants (EPCOT) Request for Applications
NAEHS Council Meeting - Open Session - February 12, 2024
NASEM Report on RNA Modifications
NIH Adds Its Voice to Call for Expanding RNA Research
Back
to Top
Last Reviewed: January 05, 2026
Skip Navigation
The Epitranscriptome
Close the left navigation
Add
Table of Contents
Introduction
What NIEHS Is Doing
NIEHS Supported Research
Grantees
Related Links
Introduction
Chemical modifications of protein, DNA, and RNA molecules play critical roles in regulating gene expression. Emerging evidence suggests post-transcriptional RNA modifications have major roles in multiple basic biological processes. Epitranscriptomics (also called RNA epigenetics) can be defined as all RNA modifications that exist within a cell. Just as epigenetic modifications regulate gene expression by modulating DNA accessibility, epitranscriptomic changes regulate gene expression by affecting RNA stability, localization, and processing. These chemical modifications are controlled by proteins that function as readers, writers, and erasers (RWEs). Writers and erasers can add or remove specific modifications, respectively, while readers interpret and process them. Studies in yeast, fruit flies, rodents and human models demonstrate that stressors can induce RNA modifications, with specific reprogramming of some regulatory RNAs.
What NIEHS Is Doing
Over 170 RNA base modifications have been identified. (Source: McCown PJ, Ruszkowska A, Kunkler CN, Breger K, Hulewicz JP, Wang MC, Springer NA, Brown JA. 2020. Naturally occurring modified ribonucleosides. Wiley Interdiscip Rev RNA 11(5):e1595. [
Abstract
])
The NIEHS environmental epitranscriptomics portfolio supports research focused on how environmental exposures affect the epitranscriptome and related health impacts. So far, over 170 RNA base modifications have been identified that have far-reaching impacts on molecular pathways associated with the development and progression of adverse health outcomes. Researchers are using a variety of methods, including cell cultures, animal models and population-based approaches to determine how environmental toxicants impact RNA biology and human health. Changes to the epitranscriptome are also being studied as potential biomarkers of exposure and exposure-induced pathologies.
The portfolio currently has approximately 40 active grants that examine a number of exposures including metals (As, Ni), phosphate, UVB, vinyl chloride, high fat diets (HFDs), and agents that induce reactive oxygen species (ROS). These grants cover a range of health outcomes such as transgenerational metabolic outcomes, lung and cardiovascular disease, cancers, neurodevelopmental and neurodegenerative disorders. There are currently over 100 diseases that are associated with aberrant epitranscriptomic processes. How environmental exposures could impact epitranscriptomics and related disorders is an ongoing area of research.
As our ability to sequence and analyze the epitranscriptome evolves, so too will the research that NIEHS supports. NIEHS-funded environmental epitranscriptomics research could enhance our understanding of how environmental factors influence human health and change how we diagnose and treat disease.
NIEHS Supported Research
Readers, writers, and erasers regulate RNA modifications and their roles in the cell.(Source: Uddin MB, Wang Z, Yang C. 2020. Dysregulations of Functional RNA Modifications in Cancer, Cancer Stemness and Cancer Therapeutics. Theranostics 10(7):3164-3189. [
Abstract
])
Stress and the Epitranscriptome
The ability of the epitranscriptome to respond to stress is vital for health and survival. One of the most prevalent RNA modifications, m6A, regulates mRNA stability, processing, localization, and translation efficiency depending on its location within the mRNA strand. In response to oxidative stress, the writer proteins METTL3/METTL14 deposit m6A, inducing upregulation of antioxidant genes. DNA damage resulting from UV irradiation also leads to m6A being recruited to the damaged sites and facilitating repair mechanisms. Other reader and writer proteins can also regulate protein translation and lipid metabolism in response to stress.
Exposures and Disease
Environmental exposures can cause changes in the epitranscriptome that contribute to disease pathology, such as liver disease and cancer. METTL3, METTL14, and FTO are writers that deposit m6A on RNA molecules. Overexpression occurs often in cancerous tissues and is associated with worse outcomes in cancer patients. RWEs and m6A dysregulation can be driven by toxic metal exposures such as arsenic, hexavalent chromium, and cadmium. Aberrant m6A modifications play a key role in carcinogenesis and the adverse health outcomes caused by these exposures. METTL3 and FTO have increased expression in fatty liver disease and drive increased m6A profiles in genes important for lipid metabolism. These proteins are impacted by a high fat diet and other exposures, such as vinyl chloride and polychlorinated biphenyls.
Transfer RNA (tRNA) plays a key role in protein translation and is heavily modified. These modifications affect tRNA structure, stability, and function, leading to significant effects on protein translation. Mutations in the enzymes that regulate tRNA modifications can cause multiple types of disorders such as cancer, neurological disorders, and mitochondrial diseases. Of the 75 proteins that have been found to regulate tRNA modifications, 54 have been associated with tRNA modopathies.
Epitranscriptomics and Development
METTL3 is critical during early development as m6A modifications are critical for regulating maternally deposited mRNA in early development. m6A readers and writers are involved in neurodevelopment and important for processes such as neuron differentiation, axon guidance, and astrocyte proliferation. How early exposures might impact the epitranscriptome and drive developmental defects is an ongoing area of study.
Similar to DNA methylation, RNA modifications can also be passed down from parent to offspring. Recent studies have shown that small RNAs in sperm can be passed from one generation to the next. Environmental exposures can modify sperm RNA which contribute to offspring phenotypes in a process referred to as transgenerational inheritance.
Grantees
Project Title
Principal Investigator
Institution
Grant Number
ALKBH5 and Nickel-Induced Lung Carcinogenesis
Hong Sun, Ph.D.
New York University School of Medicine
R21ES034811-02
Chemical Biology of DNA and RNA Alkylation
Yinsheng Wang, Ph.D.
University of California Riverside
R35ES031707
Decoding the Signature of Sperm RNA & RNA Modification of Environmental Stressors on the Intergenerational Transmission of Metabolic Phenotypes
Qi Chen, Ph.D.
University of Utah
R01ES032024-05
Determining the Role of RNA abasic Sites in Gene Regulation
Vivian Cheung, Ph.D.
Brown University
R21ES034919-02
Dysregulations of Functional RNA Modifications and Hexavalent Chromium Lung Carcinogenesis
Chengfeng Yang, Ph.D.
State University of New York at Stony Brook
R01ES032787-04
Epitranscriptomic Mechanism of Environmental Stress Response and Tumorigenesis
Yu-Ying He, Ph.D.
University of Chicago
R35ES031693-02
Functional Alterations of the Dihydrouridine Landscape in Response to Environmental Stress
Wendy Gilbert, Ph.D.
Yale University
R21ES031525-02
Functional RNA Modifications, Micronutrient Exposure, Developmental Disabilities
Hehuang Xie, Ph.D.
Virginia Polytechnic Institute and State University
R01ES031521-05
Heavy Metal-Stimulated Signal Transduction: New Metal-Regulatory and -Responsive Mechanisms
Matthew Ross, Ph.D.
University of Chicago
K99ES034084-01A1
Imprinted Gene Regulation by
in utero
Lead Exposure in Mice
Bambarendage Pinithi Perera, Ph.D.
University of Michigan at Ann Arbor
K01ES035064-01A1
Mechanisms of Transgenerational Epigenetic Inheritance
Victor Corces, Ph.D.
Emory University
R01ES027859-07
METTL3 in Chromium-Induced Angiogenesis and Carcinogenesis
Steven McMahon, Ph.D.
Thomas Jefferson University
R01ES033197-03
MGMT Down-Regulation in the Carcinogenicity of Hexavalent Chromium
Zhishan Wang, Ph.D
State University of New York Stony Brook
R01ES029496-05
Molecular Mechanisms Underlying Metabolic Reprogramming by Paternal Benzene Exposure
Heidi Lempradl, Ph.D.
Van Andel Research Institute
R56ES034765-01A1
Modulation of RNA Binding Proteins in Xenobiotic-Induced Hepatotoxicity
Yogesh Saini, Ph.D.
North Carolina State University
R01ES033709-02
N6-Methyladenosine (m6A) Interplays with RNA and DNA Damage to Regulate DNA Repair
Yuan Liu, M.D., Ph.D.
Florida International University
R03ES035200-02
Nitric Oxide as a Novel Regulator of Alternative Splicing
Joseph Schindler, M.D., Ph.D.
Case Western Reserve University
F30ES035247-02
Novel Epitranscriptomic Mechanisms in Metal Neurotoxicity
Anumantha Gounder Kanthasamy, Ph.D.
Iowa State University
1R01ES036241
Oxidative Stress and RNA Methylation
Ricardo Aguiar, Ph.D.
University of Texas Health Science Center
R01ES031522-05
Prenatal Traffic-Related Air Pollutants, Placental Epitranscriptomics, and Child Cognition
Julie Herbstman, Ph.D.
Columbia University Health Sciences
R01ES032818-03
Pho-m6A Assay: A Phosphoselective Method to Quantify Dynamics of m6A in mRNA
Qiuying Chen, Ph.D.
Weill Medical College of Cornell University
R21ES032347-02
RNA Modifications by Paternal Exposure to Arsenic and Intergenerational Effects on Sperm Quality
Shuk-Mei Ho, Ph.D.
University of Arkansas for Medical Sciences
R01ES032675-03
Role of m6A RNA Modifications in AHR-Mediated Developmental Toxicity
Neelakanteswar Aluru, Ph.D.
Woods Hole Oceanographic Institution
R21ES035153-01
Role of PXR in EDC-Induced Cardiovascular Disease
Changcheng Zhou, Ph.D.
University of California, Riverside
R35ES035015-02
Systems-Wide Analysis of Oxidative Stress-Responsive m6A Epitranscriptome
Yi-Lan Weng, Ph.D.
The Methodist Hospital Research Institute
R01ES031511-04
The Epitranscriptome as a Novel Mechanism of Arsenic-Induced Diabetes
Ana Navas-Acien, Ph.D.
Columbia University Health Sciences
R01ES032638-04
The Placental Epitranscriptome as a Novel Mechanism Behind Prenatal Metal Mixture Exposures and Child Growth and Development
Allison Kupsco, Ph.D.
Columbia University Health Sciences
R01ES035908-01
The Role of m6A-RNA Methylation in Memory Formation and Recall and its Modulation and Influence on Long-Term Outcomes as a Consequence of Early Life Lead Exposure
Jay Schneider, Ph.D.
Thomas Jefferson University
R01ES034077-02
Translational Regulation During Cigarette Smoking-Induced Reprogramming of the tRNA Epitranscriptome,
in vitro
and in a Mouse Smoking Model
Thomas Begley, Ph.D.
State University of New York At Albany
R01ES031529-05
Translational Regulation in Exposure Biology - Xenobiotic-Induced Reprograming of tRNA Modifications and Selective Translation of Codon-Biased Response Genes in Rat and Human Models
Thomas Begley, Ph.D.
State University of New York At Albany
R01ES026856-09
Understanding mRNA Condensation and Its Role in Translational Control During Stress
Hendrik Glauninger
University of Chicago
F30ES032665-04
Using Riboglow to Define RNP Interactions in Response to Environmental Stress
Erin Richards
University of Colorado Boulder
F31ES033919-03
Related Links
Article in Science on NASEM Report
Congressional Briefing: The Urgent Need to Advance RNA Science
Decoding RNA Mysteries: A New Era for Biology and Medicine - Futurum
Environmental Epigenomics
Epitranscriptomics Crosstalks and Toxicants (EPCOT) Request for Applications
NAEHS Council Meeting - Open Session - February 12, 2024
NASEM Report on RNA Modifications
NIH Adds Its Voice to Call for Expanding RNA Research
Back
to Top
Last Reviewed: January 05, 2026