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METTL Family in Healthy and Disease. Molecular biomedicine Transcription, RNA splicing, RNA translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, RNA modifications, and protein modifications, play a crucial role in regulating gene expression. The methyltransferase-like protein (METTL) family, a constituent of the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across the cell nucleus, cytoplasm, and mitochondria. Members of the METTL family, through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting processes such as DNA replication, transcription, and mRNA translation, to participate in the maintenance of normal function or promote disease development. This review primarily examines the involvement of the METTL family in normal cell differentiation, the maintenance of mitochondrial function, and its association with tumor formation, the nervous system, and cardiovascular diseases. Notably, the METTL family is intricately linked to cellular translation, particularly in its regulation of translation factors. Members represent important molecules in disease development processes and are associated with patient immunity and tolerance to radiotherapy and chemotherapy. Moreover, future research directions could include the development of drugs or antibodies targeting its structural domains, and utilizing nanomaterials to carry miRNA corresponding to METTL family mRNA. Additionally, the precise mechanisms underlying the interactions between the METTL family and cellular translation factors remain to be clarified. 10.1186/s43556-024-00194-y
A Novel Localization of METTL7A in Bergmann Glial Cells in Human Cerebellum. International journal of molecular sciences Methyltransferase-like protein 7A (METTL7A) is a member of the METTL family of methyltransferases.Little information is available regarding the cellular expression of METTL7A in the brain. METTL7A is commonly located in the endoplasmic reticulum and to a lesser extent, in the lipid droplets of some cells. Several studies have reported altered protein and RNA levels in different brain areas in schizophrenia. One of these studies found reduced protein levels of METTL7A in the cerebellar cortex in schizophrenia and stress murine models. Since there is limited information in the literature about METTL7A, we characterized its cellular and subcellular localizations in the human cerebellum using immunohistochemical analysis with laser confocal microscopy. Our study reveals a novel METTL7A localization in GFAP-positive cells, with higher expression in the end-feet of the Bergmann glia, which participate in the cerebrospinal fluid-brain parenchyma barrier. Further 3D reconstruction image analysis showed that METTL7A was expressed in the contacts between the Bergmann glia and Purkinje neurons. METTL7A was also detected in lipid droplets in some cells in the white matter. The localization of METTL7A in the human cerebellar glia limitans could suggest a putative role in maintaining the cerebellar parenchyma homeostasis and in the regulation of internal cerebellar circuits by modulating the synaptic activity of Purkinje neurons. 10.3390/ijms24098405
Differential Proteomic Analysis of the Hippocampus in Rats with Neuropathic Pain to Investigate the Use of Electroacupuncture in Relieving Mechanical Allodynia and Cognitive Decline. Gong Degui,Yu Xiangmei,Jiang Menghong,Li Changzheng,Wang Zhifu Neural plasticity Abnormal changes in hippocampal function and neuroplasticity are involved in neuropathic pain, which induces hyperalgesia and learning and memory deficits. Previous studies from our group have shown that electroacupuncture at Huantiao (GB30) and Yanglingquan (GB34) has an obvious analgesic effect on neuropathic pain. However, the central regulatory mechanism occurring in the hippocampus remains to be investigated. In this study, behavioral and proteomic analyses were performed to identify differentially expressed hippocampal proteins involved in electroacupuncture-induced analgesia. Our results showed both upregulated (TMEM126A, RDH13, and Luc7L) and downregulated proteins (Mettl7A, GGA1 RTKN, RSBN1, and CDKN1B). Further protein verification revealed for the first time that hippocampal TMEM126A plays an important anti-inflammatory role in the treatment of neuralgia by electroacupuncture. 10.1155/2021/5597163