Library of Epitranscriptome Focused Small Molecule Library contains 21,000 compounds.
Within the field of molecular biology, the epitranscriptome includes all the biochemical modifications of the RNA (the transcriptome) within a cell. Epitranscriptomics involves all functionally relevant changes to the transcriptome that do not involve a change in the ribonucleotide sequence. Thus, the epitranscriptome can be defined as the ensemble of such functionally relevant changes.
• A variety of abundant RNA modifications have been shown playing a critical role in gene regulation.
• “Writers”, “readers”, and “erasers” : RNA-binding proteins that perform post-transcriptional modifications and support cellular processes vital for RNA homeostasis.
• Aberrant RNA modifications are therapeutically relevant for the immune system and the central nervous system:
➢ Prompt the growth of acute myeloid leukemia cells.
➢ Associated with various neurodevelopmental and neuronal disorders – autism, epilepsy, brain development abnormalities, obesity, microcephaly, Prader-Willi syndrome, fragile X syndrome, major depressive disorder, etc.
➢ A regulatory mechanism of brain development and function.
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Above the Epitranscriptome: RNA Modifications and Stem Cell Identity. Francesco Morena, Chiara Argentati, […] Genes 9(7):329 (2018) doi: 10.3390/genes9070329
Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’. Matthias Schaefer, Utkarsh Kapoor, and Michael F. Jantsch Open Biol. 7(5): 170077 (2017) doi:10.1098/rsob.170077
Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells. Dali Han, Jun Liu, […] Nature 566, 270–274 (2019) doi:10.1038/s41586-019-0916-x
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Jeffrey J. Ishizuka, Robert T. Manguso, […] Nature 565, 43–48 (2019) doi:10.1038/s41586-018-0768-9
Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Isaia Barbieri, Konstantinos Tzelepis, […] Nature 552, 126–131 (2017) doi:10.1038/nature24678
m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program. Zhang S, Zhao BS, […] Cancer Cell. 31(4):591-606.e6 (2017) doi: 10.1016/j.ccell.2017.02.013
The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Ly P Vu, Brian F Pickering, […] Nature Medicine 23, 1369–1376 (2017) doi:10.1038/nm.4416
FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N6-Methyladenosine RNA Demethylase. Li Z, Weng H, […] Cancer Cell. 31(1):127-141 (2017) doi: 10.1016/j.ccell.2016.11.017