Non-coding RNAs are ribonucleic acids that do not encode proteins. Some non-coding RNAs are well understood (introns, UTRs, rRNA, tRNA etc.), others are much more mysterious. Recent work implicated non-coding RNAs in regulation of genes important for development and response to environment. The long term goal of this proposal is to better understand how long non-coding RNAs control genome activity by affecting chromatin structure. We will study the molecular mechanisms of RNA-mediated control of chromatin structure using a plant model organism, Arabidopsis thaliana. Plants are especially well suited for studying this conserved process because like metazoans they have complex development. They also contain specialized RNA Polymerases producing long non-coding RNAs necessary for transcriptional gene silencing. These polymerases can be mutated without affecting viability of the organism. We will use the unique opportunity to specifically manipulate production of long non-coding RNAs by mutating the polymerases to study the mechanisms of long non-coding RNA-mediated changes in chromatin structure. We will determine how long non-coding RNA controls gene activity by active nucleosome positioning. We will test if long non-coding RNA is involved in delimiting heterochromatic domains. We will also establish how long non-coding RNA affects three-dimensional structure of chromatin. Non-coding RNAs are involved in genomic imprinting, X-chromosome inactivation, regulation of homeotic genes and several other essential developmental and physiological processes. Defects in their functions are implicated in human disease. Precise control of chromatin structure is also required for proper development and has been implicated in cancer and several congenital disorders. Explaining the conserved molecular mechanisms of non-coding RNA- mediated control of chromatin structure will contribute to better understanding of disorders involving aberrant non-coding transcription and chromatin. We hope that it will contribute to the development of future treatments.

Public Health Relevance

Non-coding RNA is an important factor regulating activity of genomes. The goal of this research is to understand how long non-coding RNA controls genome activity by affecting chromatin structure. It will facilitate understanding the etiology of medical conditios involving dysfunctional non-coding transcription and/or incorrect establishment of chromatin structures, which will help develop future treatments.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular Genetics A Study Section (MGA)
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Carter, Anthony D
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University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
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Rowley, M Jordan; Rothi, M Hafiz; Böhmdorfer, Gudrun et al. (2017) Long-range control of gene expression via RNA-directed DNA methylation. PLoS Genet 13:e1006749
Böhmdorfer, Gudrun; Sethuraman, Shriya; Rowley, M Jordan et al. (2016) Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin. Elife 5:
Böhmdorfer, Gudrun; Wierzbicki, Andrzej T (2015) Control of Chromatin Structure by Long Noncoding RNA. Trends Cell Biol 25:623-632