Cell Rep
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Department of Immunopathology, World Premier Institute Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address:
Published: July 2023
The methyltransferase-like 3 (METTL3)-/METTL14-containing complex predominantly catalyzes N-methyladenosine (m6A) modification, which affects mRNA stability. Although the METTL14 R298P mutation is found in multiple cancer types, its biological effects are not completely understood. Here, we show that the heterozygous R298P mutation promotes cancer cell proliferation, whereas the homozygous mutation reduces proliferation. Methylated RNA immunoprecipitation sequencing analysis indicates that the R298P mutation reduces m6A modification at canonical motifs. Furthermore, this mutation induces m6A modification at aberrant motifs, which is evident only in cell lines harboring the homozygous mutation. The aberrant recognition of m6A modification sites alters the methylation efficiency at surrounding canonical motifs. One example is c-MET mRNA, which is highly methylated at canonical motifs close to the aberrantly methylated sites. Consequently, c-MET mRNA is severely destabilized, reducing c-Myc expression and suppressing cell proliferation. These data suggest that the METTL14 R298P mutation affects target recognition for m6A modification, perturbing gene expression patterns and cell growth.
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http://dx.doi.org/10.1016/j.celrep.2023.112688 | DOI Listing |
Gastroenterol Res Pract
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Despite N-methyladenosine (mA) being closely involved in various pathophysiological processes, its potential role in liver injury is largely unknown. We designed the current research to study the potential role of fat mass and obesity-associated protein (FTO), an mA demethylase, on hepatic ischemia-reperfusion injury (IRI). Wild-type mice injected with an adeno-associated virus carrying fat mass and obesity-associated protein (AAV-FTO) or adeno-associated virus carrying green fluorescent protein (GFP) (AAV-GFP) were subjected to a hepatic IRI model in vivo.
View Article and Find Full Text PDFKaohsiung J Med Sci
January 2025
Department of Gastrointestinal Surgery Center, Weifang People's Hospital, Weifang, China.
The RNA-binding protein hnRNPA2B1 acts as an m6A reader and plays a role in tumor development. This study investigates the potential mechanism of hnRNPA2B1 in colorectal cancer (CRC) progression. The expression profiles of hnRNPA2B1, circCDYL, and PHF8 in CRC cell lines were analyzed.
View Article and Find Full Text PDFDev Cell
January 2025
Department of Biological Sciences and Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117543, Singapore. Electronic address:
N-methyladenosine (mA) RNA modification and its effectors control various plant developmental processes, yet whether and how these effectors are transcriptionally controlled to confer functional specificity so far remain elusive. Herein, we show that a rice C2H2 zinc-finger protein, OsZAF, specifically activates the expression of OsFIP37 encoding a core component of the mA methyltransferase complex during microsporogenesis in rice anthers. OsFIP37, in turn, facilitates mA modification and stabilization of an auxin biosynthesis gene OsYUCCA3 to promote auxin biosynthesis in anthers.
View Article and Find Full Text PDFDev Cell
January 2025
State Key Laboratory of Efficient Production of Forest Resources, Beijing Forestry University, Beijing 100083, China; The Key Laboratory for Silviculture and Conservation of Ministry of Education, Beijing Forestry University, Beijing 100083, China; Ecological Observation and Research Station of Heilongjiang Sanjiang Plain Wetlands, National Forestry and Grassland Administration, Beijing Forestry University, Beijing 100083, China. Electronic address:
Sorbitol, a main photosynthate and transport carbohydrate in all tree fruit species in Rosaceae, acts as a signal controlling resistance against Alternaria (A.) alternata in apple by altering the expression of the MdNLR16 resistance gene via the MdWRKY79 transcription factor. However, it is not known if N-methyladenosine (mA) methylation of the mRNAs of these genes participates in the process.
View Article and Find Full Text PDFActa Pharm Sin B
December 2024
School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of -methyladenosine (mA); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown.
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