Dai et al. 2021 (PRJNA677870)

General Details

Title N7-methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression
Organism
Number of Samples 4
Release Date 2020/11/12 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP292287
ENA SRP292287
GEO GSE161319
BioProject PRJNA677870

Publication

Title
Authors Dai Z,Liu H,Liao J,Huang C,Ren X,Zhu W,Zhu S,Peng B,Li S,Lai J,Liang L,Xu L,Peng S,Lin S,Kuang M
Journal Molecular cell
Publication Date 2021 Aug 19
Abstract Cancer cells selectively promote translation of specific oncogenic transcripts to facilitate cancer survival and progression, but the underlying mechanisms are poorly understood. Here, we find that N 7 -methylguanosine (m 7 G) tRNA modification and its methyltransferase complex components, METTL1 and WDR4, are significantly upregulated in intrahepatic cholangiocarcinoma (ICC) and associated with poor prognosis. We further reveal the critical role of METTL1/WDR4 in promoting ICC cell survival and progression using loss- and gain-of-function assays in vitro and in vivo. Mechanistically, m 7 G tRNA modification selectively regulates the translation of oncogenic transcripts, including cell-cycle and epidermal growth factor receptor (EGFR) pathway genes, in m 7 G-tRNA-decoded codon-frequency-dependent mechanisms. Moreover, using overexpression and knockout mouse models, we demonstrate the crucial oncogenic function of Mettl1-mediated m 7 G tRNA modification in promoting ICC tumorigenesis and progression in vivo. Our study uncovers the important physiological function and mechanism of METTL1-mediated m 7 G tRNA modification in the regulation of oncogenic mRNA translation and cancer progression. Copyright © 2021 Elsevier Inc. All rights reserved.
PMC
PMID 34352206
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR14824509 PRJNA677870 Homo sapiens wild type
SRR14824510 PRJNA677870 Homo sapiens wild type Ribo-Seq
SRR14824511 PRJNA677870 Homo sapiens Mettl1 knockdown
SRR14824512 PRJNA677870 Homo sapiens Mettl1 knockdown Ribo-Seq
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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