Molecular mechanisms that control gene function and cell behavior are central to our understanding of and exerting influence on how biological systems integrate system- wide information for growth, development and adaptation. In contrast to DNA and protein, the epigenetics of RNA is a much less explored area. We propose that post- transcriptional RNA modifications could be functionally analogous to post-translational protein modifications. The extent of RNA modifications could depend on the physiological state of the cell. The simultaneous presence of distinctly modified RNA species, all derived from the same gene, would greatly increase the number of functional RNAs that can perform subtle or even significantly different tasks. RNA modification may represent a fundamental source of epigenetic diversity in biological regulation.
We aim to discover whether post-transcriptional modifications in biological RNAs are reversible in the cell, to identify the biological RNA targets and the enzymes that catalyze the reversal reactions. We will develop new, high throughput methods to address these questions in /E. coli/ and in human cells.

Public Health Relevance

Epigenetics controls gene expression through chemical modifications of DNA, RNA and proteins.
We aim to discover the importance of epigenetics of RNA, in order to fully understand how human cells respond and adapt to varying physiological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM088599-04
Application #
8309287
Study Section
Special Emphasis Panel (ZGM1-CBB-7 (EU))
Program Officer
Bender, Michael T
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$291,500
Indirect Cost
$95,480
Name
University of Chicago
Department
Biochemistry
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Liu, Nian; Pan, Tao (2015) RNA epigenetics. Transl Res 165:28-35
Fu, Ye; Dominissini, Dan; Rechavi, Gideon et al. (2014) Gene expression regulation mediated through reversible m?A RNA methylation. Nat Rev Genet 15:293-306
Wang, Xiao; Lu, Zhike; Gomez, Adrian et al. (2014) N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 505:117-20
Liu, Jianzhao; Yue, Yanan; Han, Dali et al. (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol 10:93-5
Liu, Nian; Parisien, Marc; Dai, Qing et al. (2013) Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA. RNA 19:1848-56
Vilfan, Igor D; Tsai, Yu-Chih; Clark, Tyson A et al. (2013) Analysis of RNA base modification and structural rearrangement by single-molecule real-time detection of reverse transcription. J Nanobiotechnology 11:8
Fu, Ye; Jia, Guifang; Pang, Xueqin et al. (2013) FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun 4:1798
Pan, Tao (2013) N6-methyl-adenosine modification in messenger and long non-coding RNA. Trends Biochem Sci 38:204-9
Jia, Guifang; Fu, Ye; He, Chuan (2013) Reversible RNA adenosine methylation in biological regulation. Trends Genet 29:108-15
Parisien, Marc; Yi, Chengqi; Pan, Tao (2012) Rationalization and prediction of selective decoding of pseudouridine-modified nonsense and sense codons. RNA 18:355-67

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