METTL5, a methyltransferase, is responsible for installing N6-methyladenosine (m6A) modification on 18S rRNA. This modification participates in regulating ribosome synthesis, mRNA translation, and is involved in multiple biological processes such as cell differentiation, development, and metabolism [3,4]. Mutations or deletions of Mettl5 can lead to abnormal translation and gene expression, affecting stem cell behaviors [4].

In multiple cancer types, METTL5 shows oncogenic properties. In hepatocellular carcinoma (HCC), METTL5 promotes glucose metabolic reprogramming, cell proliferation, and metastasis by stabilizing c-Myc through facilitating USP5 translation [1]. In intrahepatic cholangiocarcinoma (ICC), METTL5-mediated 18S rRNA m6A modification promotes oncogenic mRNA translation and tumor progression [2]. In gastric cancer, METTL5 promotes cancer cell proliferation, migration, invasion, and confers cisplatin resistance via sphingomyelin metabolism [5]. In addition, Mettl5 knockout mice exhibit poor ossification, widened cranial sutures, and decreased osteogenic differentiation of suture mesenchymal stem cells, suggesting its role in craniofacial development [6].

In conclusion, METTL5 is crucial in ribosomal RNA methylation, influencing mRNA translation and various biological processes. Its dysregulation is associated with cancer progression and craniofacial developmental diseases. The study of METTL5 knockout mouse models has provided valuable insights into its functions in these disease areas, helping to understand the underlying molecular mechanisms and potentially offering new therapeutic targets.

References:

1. Xia, Peng, Zhang, Hao, Lu, Haofeng, Zhang, Zhonglin, Yuan, Yufeng. 2023. METTL5 stabilizes c-Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression. In Cancer communications (London, England), 43, 338-364. doi:10.1002/cac2.12403. https://pubmed.ncbi.nlm.nih.gov/36602428/

2. Dai, Zihao, Zhu, Wanjie, Hou, Yingdong, Lin, Shuibin, Kuang, Ming. 2023. METTL5-mediated 18S rRNA m6A modification promotes oncogenic mRNA translation and intrahepatic cholangiocarcinoma progression. In Molecular therapy : the journal of the American Society of Gene Therapy, 31, 3225-3242. doi:10.1016/j.ymthe.2023.09.014. https://pubmed.ncbi.nlm.nih.gov/37735874/

3. van Tran, Nhan, Ernst, Felix G M, Hawley, Ben R, Graille, Marc, Lafontaine, Denis L J. . The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. In Nucleic acids research, 47, 7719-7733. doi:10.1093/nar/gkz619. https://pubmed.ncbi.nlm.nih.gov/31328227/

4. Turkalj, Elena M, Vissers, Caroline. 2022. The emerging importance of METTL5-mediated ribosomal RNA methylation. In Experimental & molecular medicine, 54, 1617-1625. doi:10.1038/s12276-022-00869-y. https://pubmed.ncbi.nlm.nih.gov/36266443/

5. Zhang, Ya-Qiong, Li, Jian, Qin, Zhe, Zhang, Xiao-Hong, Feng, Li. . METTL5 promotes gastric cancer progression via sphingomyelin metabolism. In World journal of gastrointestinal oncology, 16, 1925-1946. doi:10.4251/wjgo.v16.i5.1925. https://pubmed.ncbi.nlm.nih.gov/38764837/

6. Lei, Kexin, Xu, Ruoshi, Wang, Qian, Zhou, Chenchen, Yuan, Quan. 2022. METTL5 regulates cranial suture fusion via Wnt signaling. In Fundamental research, 3, 369-376. doi:10.1016/j.fmre.2022.04.005. https://pubmed.ncbi.nlm.nih.gov/38933773/