Vu et al. 2017 (PRJNA385767)

General Details

Title miCLIP, RNA-Seq, and Ribo-Seq in MOLM13 cells
Organism
Number of Samples 18
Release Date 2017/05/08 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP106608
ENA SRP106608
GEO GSE98623
BioProject PRJNA385767

Publication

Title
Authors Vu LP,Pickering BF,Cheng Y,Zaccara S,Nguyen D,Minuesa G,Chou T,Chow A,Saletore Y,MacKay M,Schulman J,Famulare C,Patel M,Klimek VM,Garrett-Bakelman FE,Melnick A,Carroll M,Mason CE,Jaffrey SR,Kharas MG
Journal Nature medicine
Publication Date 2017 Nov
Abstract N 6 -methyladenosine (m 6 A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m 6 A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m 6 A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth. METTL3 mRNA and protein are expressed more abundantly in acute myeloid leukemia (AML) cells than in healthy HSPCs or other types of tumor cells. Furthermore, METTL3 depletion in human myeloid leukemia cell lines induces cell differentiation and apoptosis and delays leukemia progression in recipient mice in vivo. Single-nucleotide-resolution mapping of m 6 A coupled with ribosome profiling reveals that m 6 A promotes the translation of c-MYC, BCL2 and PTEN mRNAs in the human acute myeloid leukemia MOLM-13 cell line. Moreover, loss of METTL3 leads to increased levels of phosphorylated AKT, which contributes to the differentiation-promoting effects of METTL3 depletion. Overall, these results provide a rationale for the therapeutic targeting of METTL3 in myeloid leukemia.
PMC PMC5677536
PMID 28920958
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR5515143 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515132 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515133 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515134 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515135 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515136 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515137 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515138 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515139 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515140 PRJNA385767 Homo sapiens Acute myeloid leukemia RNA-Seq
SRR5515141 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515142 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515144 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515145 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515146 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515147 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515148 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
SRR5515149 PRJNA385767 Homo sapiens Acute myeloid leukemia Ribo-Seq Harringtonine
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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