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We are analyzing https://www.nature.com/articles/s41467-018-03513-4.

Title:
RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia | Nature Communications
Description:
The roles of RNA 5-methylcytosine (RNA:m5C) and RNA:m5C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure. In contrast, NSUN1 binds BRD4 and RNA-polymerase-II to form an active chromatin structure that is insensitive to 5-AZA, but hypersensitive to the BRD4 inhibitor JQ1 and to the downregulation of NSUN1 by siRNAs. Both 5-AZA-resistant leukaemia cell lines and clinically 5-AZA-resistant myelodysplastic syndrome and acute myeloid leukaemia specimens have a significant increase in RNA:m5C and NSUN1-/BRD4-associated active chromatin. This study reveals novel RNA:m5C/RCMT-mediated chromatin structures that modulate 5-AZA response/resistance in leukaemia cells, and hence provides a new insight into treatment of leukaemia. Resistance to chemotherapy is a serious issue that can be influenced by RNA epigenetics and chromatin structure. Here, the authors show in leukaemia cells that RNA 5-methylcytosine (RNA:m5C) and RNA:m5C methyltransferases (RCMTs) mediate chromatin structures that can modulate 5-Azacitidine response and resistance.
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Keywords {πŸ”}

cells, fig, leukaemia, pubmed, rna, nsun, hnrnpk, article, aza, chromatin, ocim, google, scholar, rnapolii, cas, cell, azaresistant, azasensitive, bone, mar, brd, ctdsp, supplementary, active, dna, spipu, interactions, marrow, data, dnmt, buffer, clinical, gata, specimens, rcmts, expression, proteins, analysis, cancer, min, central, nature, sirnas, demonstrated, performed, lines, gene, tet, increased, colocalization,

Topics {βœ’οΈ}

nature portfolio anti-rna-pol-ii ctd-s2p antibody bound rna-pol-ii ctd-s2p privacy policy rna-pol-ii ctd-s2/s5p rna-pol-ii ctdβˆ’s2pβˆ’nsun1 interaction active rna-pol-ii ctd-s2p rna-pol-ii ctd-s2p compared including rna-pol-ii ctd-s2p institutional research grant research/education fund rna-pol-ii crd-s2p active rna-pol-ii recruitment rna-pol-ii ctd-s2p 5-aza-resistant aml/mds specimens rna-pol-ii ctd kinases active rna-pol-ii complex advertising rna-pol-ii/cdk9/7 complex recruit active rna-pol-ii rna-pol-ii ctd-s5p fam-rna oligo/hnrnpk/antibody-agarose beads 5-aza-resistant mds/aml cases cdk9/p-tefb-dependent phosphorylation 5-aza-sensitive aml/mds cases rna-pol-ii recruitment thermofisher scientific company clinical mds/aml specimens tissue culture media pathogenic nsun1/nol1-e2a fusion rna-pol-ii ctd solutions reprints dose-dependent rnase-induced disruption nature nature 468 nature 526 nature 503 brd4-bound cdk9/p-tefb 5-aza-resistant bone marrows active rna-pol-ii active rna pol-ii selective 5-aza-/rnase-sensitive interactions rna-pol-ii ctds2p recruits rna-pol-ii m5c/rcmt-mediated chromatin structures recruit rna-polymerase-ii rna-pol-ii s5p ctsa-ita core subsidies originally 5-aza-sensitive oci-m2

Schema {πŸ—ΊοΈ}

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      headline:RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia
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