Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05880
[1]
Non-coding RNA MALAT1 WTAP  lncRNA       miRNA   circRNA Direct Enhancement m6A modification PML-RARalpha PML-RARalpha WTAP Methylation : m6A sites
m6A Modification:
m6A Regulator Wilms tumor 1-associating protein (WTAP) WRITER
m6A Target Retinoic Acid Receptor Alpha-Retinoic Acid Receptor Alpha (PML-RARalpha)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) LncRNA View Details
Regulated Target Pre-mRNA-splicing regulator WTAP (WTAP) View Details
Crosstalk Relationship ncRNA  →  m6A Enhancement
Crosstalk Mechanism ncRNAs directly impacts m6A modification through recruiting m6A regulator
Crosstalk Summary MALAT1 hijacks both the chimeric mRNAs and fusion proteins in nuclear speckles during chromosomal translocations and mediates the colocalization of oncogenic fusion proteins with METTL14. MALAT1 and fusion protein complexes serve as a functional loading bridge for the interaction of Retinoic Acid Receptor Alpha-Retinoic Acid Receptor Alpha (PML-RARalpha) mRNA, METTL14, METTL3 and WTAP. MALAT1 regulates chimeric mRNA export in a manner dependent on the YTHDC1 and SRSF3
Responsed Disease Blood malignancies ICD-11: 2B33.Y
Cell Process Cell differentiation
In-vitro Model
NB4 Acute promyelocytic leukemia Homo sapiens CVCL_0005
MOLM-13 Adult acute myeloid leukemia Homo sapiens CVCL_2119
Kasumi-1 Myeloid leukemia with maturation Homo sapiens CVCL_0589
HL-60 Adult acute myeloid leukemia Homo sapiens CVCL_0002
K-562 Chronic myelogenous leukemia Homo sapiens CVCL_0004
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model The tumor xenografts were established by a single intraperitoneal transplantation of 5 × 106 NB4 cells in 0.2 ml of PBS into NOD-SCID mice. The NOD-SCID mice were intravenously (tail vein) implanted with sh-RNA-established NB4 cells. Direct injection of 5 × 106 shRNA-transformed NB4 cells into 150 μL of PBS was performed to establish intravenous (tail vein) leukemia.
References
Ref 1 Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop in blood malignancies. Cell Death Dis. 2020 Jul 23;11(7):566. doi: 10.1038/s41419-020-02795-1.