Sepich-Poore et al. 2021 (PRJNA729866)

General Details

Title Mapping translation in wild-type and METTL5 knockout (KO) HepG2 cells
Organism
Number of Samples 4
Release Date 2021/05/13 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP319885
ENA SRP319885
GEO
BioProject PRJNA729866

Publication

Title
Authors Sepich-Poore C,Zheng Z,Schmitt E,Wen K,Zhang ZS,Cui XL,Dai Q,Zhu AC,Zhang L,Sanchez Castillo A,Tan H,Peng J,Zhuang X,He C,Nachtergaele S
Journal The Journal of biological chemistry
Publication Date 2022 Mar
Abstract Ribosomal RNAs (rRNAs) have long been known to carry chemical modifications, including 2'O-methylation, pseudouridylation, N 6 -methyladenosine (m 6 A), and N 6,6- dimethyladenosine. While the functions of many of these modifications are unclear, some are highly conserved and occur in regions of the ribosome critical for mRNA decoding. Both 28S rRNA and 18S rRNA carry single m 6 A sites, and while the methyltransferase ZCCHC4 has been identified as the enzyme responsible for the 28S rRNA m 6 A modification, the methyltransferase responsible for the 18S rRNA m 6 A modification has remained unclear. Here, we show that the METTL5-TRMT112 methyltransferase complex installs the m 6 A modification at position 1832 of human 18S rRNA. Our work supports findings that TRMT112 is required for METTL5 stability and reveals that human METTL5 mutations associated with microcephaly and intellectual disability disrupt this interaction. We show that loss of METTL5 in human cancer cell lines and in mice regulates gene expression at the translational level; additionally, Mettl5 knockout mice display reduced body size and evidence of metabolic defects. While recent work has focused heavily on m 6 A modifications in mRNA and their roles in mRNA processing and translation, we demonstrate here that deorphanizing putative methyltransferase enzymes can reveal previously unappreciated regulatory roles for m 6 A in noncoding RNAs. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PMC PMC8857481
PMID 35033535
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR14525704 PRJNA729866 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR14525705 PRJNA729866 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR14525706 PRJNA729866 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR14525707 PRJNA729866 Homo sapiens HepG2 Ribo-Seq Cycloheximide
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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