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Results for “Methyltransferase-like 5”

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PubMed2025

Modulation of Mettl5 alleviates airway allergy by regulating the epigenetic profile of M2 macrophages.

M2 macrophages (M2 cells) are known to be involved in both Th2 responses and immune regulation. However, the underlying mechanisms remain unclear. Functional abnormalities in macrophages are associated with airway allergy (AA). The objective of this study was to investigate the role of methyltransferase-like 5 (Mettl5) in macrophages and its potential to alleviate AA. In this study, an airway allergy (AA) mouse model was established using dust mite extracts (DME) as the specific antigen. M2 cells were collected from mice with and without AA. The role of Mettl5 in modulating the immune activities of M2 cells was assessed using both epigenetic and immunological approaches. We found that Mettl5 levels were elevated in airway M2 cells from mice with AA. The presence of Mettl5 in airway M2 cells was positively correlated with airway Th2 polarization in these mice. Airway M2 cells from AA mice exhibited impaired immune-suppressive function, which was resolved by ablating the Mettl5 gene in macrophages. Mettl5 was responsible for the hypermethylation of the Il10 promoter in airway M2 cells of AA mice. Exposure to DME induced Mettl5, which in turn recruited USP21 to deubiquitinate GATA3, thereby boosting IL-4 expression in M2 cells. Inhibiting Mettl5 restored the immune-suppressive capacity of airway M2 cells and mitigated experimental AA. In conclusion, Mettl5 plays a critical role in subverting the immune-regulatory capacity and enhancing IL-4 expression in M2 cells. Inhibition of Mettl5 can mitigate experimental AA by restoring the immune-regulatory functions of M2 cells.

Animals↗

PubMed2026

Pathomics-based machine learning models for predicting METTL5 expression and prognosis in lung adenocarcinoma.

BACKGROUND: METTL5, an N6-methyladenosine (m6A) RNA methyltransferase, has been implicated in tumor progression, but its prognostic value and non-invasive prediction in lung adenocarcinoma (LUAD) remain unclear. This study aimed to develop a pathomics-based machine learning model to predict METTL5 expression from histopathological images and evaluate its prognostic significance in LUAD. METHODS: A total of 327 LUAD patients from The Cancer Genome Atlas (TCGA) with matched hematoxylin and eosin (H&E) slides, transcriptomic, and clinical data were included and randomly divided into training and validation sets (7:3). Quantitative histopathological features were extracted using PyRadiomics. Feature selection was performed via maximum relevance minimum redundancy (mRMR) and recursive feature elimination (RFE), followed by construction of a Gradient Boosting Machine (GBM) model. A pathomics score (PS) was generated to assess prognostic relevance. Survival analyses, gene set variation analysis (GSVA), tumor mutational burden (TMB), immune infiltration analysis, and in vitro functional assays were conducted. RESULTS: METTL5 overexpression was independently associated with poor overall survival [hazard ratio (HR) =1.637, P=0.007]. The model achieved good predictive performance [area under the curve (AUC) =0.847 in the training set and 0.752 in the validation set]. High PS was significantly associated with worse survival and remained an independent prognostic factor (HR =1.563, P=0.03). Elevated PS correlated with altered metabolic pathways, increased TMB, and immune microenvironment changes. METTL5 knockdown reduced proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. CONCLUSIONS: The pathomics-based model accurately predicts METTL5 expression and provides prognostic stratification in LUAD, supporting its potential as a practical imaging-derived biomarker.

Methyltransferase-like 5↗

PubMed2000

Detection of beet yellows closterovirus methyltransferase-like and helicase-like proteins in vivo using monoclonal antibodies.

In the positive-stranded RNA genome of beet yellows closterovirus (BYV), the 5'-terminal ORF 1a encodes a 295 kDa polyprotein with the domains of papain-like cysteine proteinase, methyltransferase (MT) and helicase (HEL), whereas ORF 1b encodes an RNA-dependent RNA polymerase. Eleven and five hybridoma cell lines secreting monoclonal antibodies (MAbs) were derived from mice injected with the bacterially expressed fragments of the BYV 1a product encompassing the MT and HEL domains, respectively. On immunoblots of protein from BYV-infected Tetragonia expansa plants, four MAbs against the MT recognized a approximately 63 kDa protein, and two MAbs against the HEL recognized a approximately 100 kDa protein. Both the methyltransferase-like protein and the helicase-like protein were found mainly in the fractions of large organelles (P1) and membranes (P30) of the infected plants. These data clearly indicate that (i) the BYV methyltransferase-like and helicase-like proteins, like other related viral enzymes, are associated with membrane compartments in cells, and (ii) the 1a protein, apart from the cleavage by the leader papain-like proteinase that is expected to produce the 66 kDa and 229 kDa fragments, undergoes additional processing by a virus-encoded or cellular proteinase.

Amino Acid Sequence↗

PubMed2025

The impact of m6A methyltransferase METTL3 on airway remodeling in bronchial asthma.

BACKGROUND: Methyltransferase-like 3 (METTL3) is known to play a role in asthma airway remodeling and cell proliferation. Adenylate kinase 4 (AK4) regulates the proliferation of pulmonary artery smooth muscle cells and exerts its effects through the protein kinase B (AKT) pathway. However, the role of METTL3 and AK4-AKT in bronchial smooth muscle cells remains unclear. METHODS: Systemic METTL3 knockout mice and a mouse model of asthma were established. Airway remodeling was assessed using pulmonary function tests, histopathological staining, and Western blot analysis. RNA sequencing (RNA-seq) was performed to detect changes in gene expression following METTL3 knockdown. The 5-ethynyl-2'-deoxyuridine (EdU) assay was used to evaluate cell proliferation. Finally, the expression levels of relevant proteins were validated by Western blotting. RESULTS: Compared with the control model group, the METTL3 knockout group showed significantly reduced inflammatory cell infiltration, decreased collagen fiber deposition, and attenuated airway smooth muscle hyperplasia. RNA-seq revealed that the expression of numerous proliferation-related genes, including AK4, was upregulated following METTL3 knockdown. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these genes were primarily enriched in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. The EdU assay demonstrated that METTL3 knockdown inhibited cell proliferation. Western blot validation showed increased AK4 expression in lung tissues of the METTL3 knockout group compared to the control group, while phosphorylated AKT (p-AKT) levels were reduced. CONCLUSIONS: METTL3 knockout inhibits airway smooth muscle hyperplasia and alleviates airway remodeling in asthma. This effect may be mediated through the regulation of AK4 and the AKT signaling pathway.

Airway Remodeling↗

PubMed2003

Human fibrillarin forms a sub-complex with splicing factor 2-associated p32, protein arginine methyltransferases, and tubulins alpha 3 and beta 1 that is independent of its association with preribosomal ribonucleoprotein complexes.

Fibrillarin (FIB, Nop1p in yeast) is an RNA methyltransferase found not only in the fibrillar region of the nucleolus but also in Cajal bodies. FIB is essential for efficient processing of preribosomal RNA during ribosome biogenesis, although its precise function in this process and its role in Cajal bodies remain uncertain. Here, we demonstrate that the human FIB N-terminal glycine- and arginine-rich domain (residues 1-77) and its spacer region 1 (78-132) interact with splicing factor 2-associated p32 (SF2A-p32) and that the FIB methyltransferase-like domain (133-321) interacts with protein-arginine methyltransferase 5 (PRMT5, Janus kinase-binding protein 1). We also show that these proteins associate with several additional proteins, including PRMT1, tubulin alpha 3, and tubulin beta 1 to form a sub-complex that is principally independent of the association of FIB with preribosomal ribonucleoprotein complexes that co-immunoprecipitate with the sub-complex in human cells expressing FLAG-tagged FIB. Based on the physical association of FIB with SF2A-p32 and PRMTs, as well as the other reported results, we propose that FIB may coordinate both RNA and protein methylation during the processes of ribosome biogenesis in the nucleolus and RNA editing such as small nuclear (nucleolar) ribonucleoprotein biogenesis in Cajal bodies.

Chromosomal Proteins, Non-Histone↗

PubMed1998

Genome properties of beet virus Q, a new furo-like virus from sugarbeet, determined from unpurified virus.

Based solely on the information that beet virus Q (BVQ) contains tubular particles, the entire nucleotide sequence of its tripartite genome was determined from unpurified virus in ca. 40 ml crude sap from locally infected Chenopodium quinoa. A starting sequence for RNA 1 was generated using primers corresponding to highly conserved helicase domains in the respective RNAs of furo-, pomo-, peclu-, hordei- and tobraviruses, and was extended by a walking random-primed cDNA approach. The similarity of the 3' ends of furoviral RNAs allowed starting sequences for BVQ RNAs 2 and 3 to be obtained once the 3' end of RNA 1 was known. BVQ RNA 1 encodes a protein with a methyltransferase-like, a variable and a helicase-like region, and for a readthrough protein which, in addition, contains an RNA-dependent RNA polymerase region. RNA 2 carries the coat protein gene, a coat protein read-through protein gene and two additional ORFs which may have arisen by deletions from an originally larger readthrough domain. RNA 3 carries a triple gene block resembling that of several other rod-shaped viruses. The 5' UTRs of the three RNAs have the potential to form a series of hairpins with C-A and C-C mismatches resembling those found in tymoviral RNAs. The 3' ends can be folded into tRNA-like structures which are preceded by a long hairpin-like structure and an upstream pseudoknot domain. BVQ belongs to the recently proposed genus Pomovirus; it shows evolutionary relationships to furoviruses in sensu stricto, peclu-, hordei-, tobra-, tymo-, tobamo-, carla- and potexviruses.

Amino Acid Sequence↗

PubMed2004

Complete nucleotide sequence and genome organization of Grapevine leafroll-associated virus 3, type member of the genus Ampelovirus.

This study reports on the complete genome sequence of Grapevine leafroll-associated virus 3, the type member of the genus Ampelovirus. The genome is 17 919 nt in size and contains 13 open reading frames (ORFs). Previously, the sequence of 13 154 nt of the 3'-terminal of the genome was reported. The newly sequenced portion contains a 158 nt 5' UTR, a single papain-like protease and a methyltransferase-like (MT) domain. ORF1a encodes a large polypeptide with a molecular mass of 245 kDa. With a predicted +1 frameshift, the large fusion protein generated from ORF1a/1b would produce a 306 kDa polypeptide. Phylogenetic analysis using MT domains further supports the creation of the genus Ampelovirus for mealy-bug-transmitted viruses in the family Closteroviridae.

Amino Acid Sequence↗

PubMed2001

Genome-wide hypomethylation in hepatocellular carcinogenesis.

Aberrant genome-wide hypomethylation has been thought to be related to tumorigenesis. However, its mechanism and implications in hepatocellular carcinogenesis remain to be elucidated. Samples of hepatoma (hepatocellular carcinoma, HCC) and paired non-HCC liver tissues were obtained from 17 HCC patients. Normal liver tissues obtained from three individuals were used as controls. Compared with the paired non-HCC liver tissues, genome-wide 5-methylcytosine content in HCC was reduced in all of the tested HCC samples (P < 0.001). Conversely, genome-wide 5-methylcytosine content did not significantly differ among normal, noncirrhotic, and cirrhotic liver tissues. Moreover, the degree of reduced DNA methylation was related to late histopathological HCC grade (P = 0.005) and large tumor size (P = 0.079). Compared with the paired non-HCC liver tissues, expression of DNA methyltransferases DNMT-1, DNMT-3A, and DNMT-3B and the DNA methyltransferase-like gene, DNMT-2, was up-regulated in 53, 41, 59, and 47% of the HCC samples, respectively. Surprisingly, small amounts of LINE-1 retrotransposon transcripts were detected in HCC and non-HCC as well as normal liver tissues, and the expression levels were not significantly different in HCC compared with the paired non-HCC or normal liver tissues. Of interest, the 3' ends of these LINE-1 transcripts were truncated. Our findings suggest that genome-wide hypomethylation in HCC is a continuing process that persists throughout the lifetime of the tumor cells rather than a historical event occurring in precancer stages or in cell origins for HCC. Up-regulation of DNA methyltransferases might simply be a result of increased cell proliferation in cancer. In addition, our results did not support the hypothesis of activation of transposable elements in HCC via genome-wide hypomethylation.

5-Methylcytosine↗