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Last update 08 May 2025

METTL17

Last update 08 May 2025

Basic Info

Synonyms

False p73 target gene protein, FLJ20859, Methyltransferase 11 domain-containing protein 1

+ [5]

Introduction

Mitochondrial ribosome (mitoribosome) assembly factor (PubMed:36482135, PubMed:38199006). Binds at the interface of the head and body domains of the mitochondrial small ribosomal subunit (mt-SSU), occluding the mRNA channel and preventing compaction of the head domain towards the body (PubMed:36482135). Probable inactive methyltransferase: retains the characteristic folding and ability to bind S-adenosyl-L-methionine, but it probably lost its methyltransferase activity (PubMed:38234605).

Drugs associated with METTL17

CpG-siRNAMETTL17

Target

METTL17

Mechanism

METTL17 inhibitors

Active Org.

City of Hope National Medical Center

Originator Org.

City of Hope National Medical Center

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

WO2023183906

Patent Mining

Target

METTL17

Mechanism-

Active Org.

The Broad Institute, Inc. [+1]

Originator Org.

The Broad Institute, Inc. [+1]

Active Indication

Age related disease [+2]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with METTL17

100 Translational Medicine associated with METTL17

0 Patents (Medical) associated with METTL17

Literatures (Medical) associated with METTL17

01 Jun 2025·Toxicology and Applied Pharmacology

Demethylzeylasteral inhibits osteosarcoma cell proliferation by regulating METTL17-mediated mitochondrial oxidative phosphorylation

Article

Author: Cao, Jingyu ; Wang, Chengbo ; Aziz, Faisal ; Zhu, Xiangzhan ; Wang, Zimeng ; Li, Ya ; Zhang, Haotian ; Li, Xianxiao ; Yang, Minglei ; He, Lihua

Osteosarcoma (OS) represents the most common primary bone malignancy, characterized by substantial disability and mortality, thereby underscoring the critical need for more effective therapeutic interventions to improve clinical outcomes. Demethylzeylasteral (DEM) is a bio-active compound has been reported for its anti-tumor properties through various mechanisms. Nonetheless, the specific effects of DEM on OS have yet to be fully elucidated. This study demonstrated that DEM significantly inhibited OS cell proliferation both in vitro and in vivo. Mechanistically, DEM impairs mitochondrial OXPHOS by targeting METTL17, a known regulator of mitochondrial translation, resulting in reduced ATP production. Subsequent investigations revealed that METTL17 knockdown exerts potent anti-tumor effects in OS, significantly suppressing both in vitro cell proliferation and in vivo xenograft tumor growth. Furthermore, METL17 overexpression significantly alleviated the inhibitory effects of DEM on cell proliferation, while restoring ATP production and oxygen consumption rates. These findings suggest that DEM impedes OS growth by inducing mitochondrial dysfunction through targeting METTL17, thereby highlighting a novel therapeutic strategy and potential molecular target for OS treatment.

01 Feb 2025·Pharmacogenetics and Genomics

Pharmacogenetics of tuberculosis treatment toxicity and effectiveness in a large Brazilian cohort

Article

Author: Rolla, Valeria C ; Sterling, Timothy R ; Andrade, Bruno B ; Yang, Jing ; Haas, David W ; Amorim, Gustavo ; Cordeiro-Santos, Marcelo ; Velez Edwards, Digna R ; Figueiredo, Marina C ; Jaworski, James ; Santos, Adalberto R ; Turner, Megan ; Kritski, Afrânio L

BackgroundGenetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil.MethodsParticipants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil. We included persons with culture-confirmed drug-susceptible pulmonary tuberculosis who started treatment between 2015 and 2019, and who were eligible for pharmacogenetics. Treatment included 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol, then 4 months of isoniazid and rifampin or rifabutin, with 24-month follow-up. Analyses included 43 polymorphisms in 20 genes related to antituberculosis drug hepatotoxicity or pharmacokinetics. Whole exome sequencing was done in a case-control toxicity subset.ResultsAmong 903 participants in multivariable genetic association analyses, NAT2 slow acetylator status was associated with increased risk of treatment-related grade 2 or greater adverse events, including hepatotoxicity. Treatment failure/recurrence was more likely among NAT2 rapid acetylators, but not statistically significant at the 5% level. A GSTM1 polymorphism (rs412543) was associated with increased risk of treatment-related adverse events, including hepatotoxicity. SLCO1B1 polymorphisms were associated with increased risk of treatment-related hepatoxicity and treatment failure/recurrence. Polymorphisms in NR1/2 were associated with decreased risk of adverse events and increased risk of failure/recurrence. In whole exome sequencing, hepatotoxicity was associated with a polymorphism in VTI1A, and the genes METTL17 and PRSS57, but none achieved genome-wide significance.ConclusionIn a clinical cohort representing three regions of Brazil, NAT2 acetylator status was associated with risk for treatment-related adverse events. Additional significant polymorphisms merit investigation in larger study populations, particularly regarding risk of treatment failure/recurrence.

01 Feb 2025·Journal of Biological Chemistry

Crucial role and conservation of the three [2Fe-2S] clusters in the human mitochondrial ribosome

Article

Author: Lill, Roland ; Boß, Linda ; Elsässer, Hans-Peter ; Stehling, Oliver

Mitochondria synthesize only a small set of their proteins on endogenous mitoribosomes. These particles differ in structure and composition from both their bacterial 70S ancestors and cytosolic 80S ribosomes. Recently published high resolution structures of the human mitoribosome revealed the presence of three [2Fe-2S] clusters in the small and large subunits. Each of these clusters is coordinated in a bridging fashion by cysteine residues from two different mitoribosomal proteins. Here, we investigated the cell biological and biochemical roles of all three iron-sulfur clusters in mitochondrial function and assembly. First, we found a requirement of both early and late factors of the mitochondrial iron-sulfur cluster assembly machinery for protein translation indicating that not only the mitoribosome [2Fe-2S] clusters but also the [4Fe-4S] cluster of the mitoribosome assembly factor METTL17 are required for mitochondrial translation. Second, siRNA-mediated depletion of the cluster-coordinating ribosomal proteins bS18m, mS25, or mL66 and complementation with either the respective WT or cysteine-exchange proteins unveiled the importance of the clusters for assembly, stability, and function of the human mitoribosome. As a consequence, the lack of cluster binding to mitoribosomes impaired the activity of the mitochondrial respiratory chain complexes and led to altered mitochondrial morphology with a loss of cristae membranes. Finally, in silico investigation of the phylogenetic distribution of the cluster-coordinating cysteine motifs indicated their presence in most metazoan mitoribosomes, with exception of ray-finned fish. Collectively, our study highlights the functional need of mitochondrial iron-sulfur protein biogenesis for both protein translation and respiratory energy supply in most metazoan mitochondria.

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METTL17

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