General Information of the m6A Regulator (ID: REG00017)
Regulator Name Methyltransferase-like 16 (METTL16)
Synonyms
Methyltransferase 10 domain-containing protein; RNA N6-adenosine-methyltransferase METTL16; N6-adenosine-methyltransferase METTL16; U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase; METT10D
    Click to Show/Hide
Gene Name METTL16
Sequence
MALSKSMHARNRYKDKPPDFAYLASKYPDFKQHVQINLNGRVSLNFKDPEAVRALTCTLL
REDFGLSIDIPLERLIPTVPLRLNYIHWVEDLIGHQDSDKSTLRRGIDIGTGASCIYPLL
GATLNGWYFLATEVDDMCFNYAKKNVEQNNLSDLIKVVKVPQKTLLMDALKEESEIIYDF
CMCNPPFFANQLEAKGVNSRNPRRPPPSSVNTGGITEIMAEGGELEFVKRIIHDSLQLKK
RLRWYSCMLGKKCSLAPLKEELRIQGVPKVTYTEFCQGRTMRWALAWSFYDDVTVPSPPS
KRRKLEKPRKPITFVVLASVMKELSLKASPLRSETAEGIVVVTTWIEKILTDLKVQHKRV
PCGKEEVSLFLTAIENSWIHLRRKKRERVRQLREVPRAPEDVIQALEEKKPTPKESGNSQ
ELARGPQERTPCGPALREGEAAAVEGPCPSQESLSQEENPEPTEDERSEEKGGVEVLESC
QGSSNGAQDQEASEQFGSPVAERGKRLPGVAGQYLFKCLINVKKEVDDALVEMHWVEGQN
RDLMNQLCTYIRNQIFRLVAVN
    Click to Show/Hide
Family methyltransferase superfamily; METTL16/RlmF family
Function
RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts . Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure. Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase. In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A. In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs . Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA. Specifically binds the 3'-end of the MALAT1 long non-coding RNA.
    Click to Show/Hide
Gene ID 79066
Uniprot ID
MET16_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Target Genes Click to View Potential Target Genes of This Regulator
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
METTL16 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
Cellular tumor antigen p53 (TP53/p53)
Liver cancer [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12.02]
Response Summary Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of hepatocellular carcinoma (HCC) patients. And this study found significant associations between the genetic alterations and clinicopathological features as well as Cellular tumor antigen p53 (TP53/p53) alteration.
Extracellular sulfatase Sulf-2 (Sulf2)
Injury of blood vessels of thorax [ICD-11: NB30]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Injury of pulmonary blood vessels [ICD-11: NB30.4]
Target Regulation Down regulation
In-vitro Model
Rattus norvegicus (Rat pulmonary microvascular endothelial cells (PMVECs) were isolated from lung tissues)
In-vivo Model The rats were randomly divided into a fresh air group and a COPD group and each group contained 10 rats. The COPD group was placed into a breathable cage and exposed to PM2.5 (1.46 mg/m3) from the motor vehicle exhaust for two 2-h exposure periods (from 9:00 a.m. to 11:00 a.m. and from 15:00 p.m. to 17:00 p.m.), 5 days per week, for 7 months. After each period of exposure, the animals were exposed to fresh air for 30 min to take a rest. Gasoline-powered motorcycle used as of source of the Particulate matter (PM) pollution was located next door to the rat exposure room, and the PM was directed towards the exposure room through a metal tube. Fresh air was sent to through an air pump. After exposed for 7 months, rats were performed lung function test using a Forced Pulmonary Maneuver System (Buxco Research Systems, Wilmington, NC, USA).
Response Summary METTL16 regulates Extracellular sulfatase Sulf-2 (Sulf2) expression via m6A modification and thereby contribute to PM2.5-induced pulmonary microvascular injury.
G1/S-specific cyclin-D1 (CCND1)
Gastric cancer [ICD-11: 2B72]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [3]
Responsed Disease Gastric cancer [ICD-11: 2B72]
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process G1/S blocking
In-vitro Model
SNU-719 Gastric tubular adenocarcinoma Homo sapiens CVCL_5086
SGC-7901 Gastric carcinoma Homo sapiens CVCL_0520
MKN28 Gastric tubular adenocarcinoma Homo sapiens CVCL_1416
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HGC-27 Gastric carcinoma Homo sapiens CVCL_1279
GES-1 Normal Homo sapiens CVCL_EQ22
AGS Gastric adenocarcinoma Homo sapiens CVCL_0139
In-vivo Model Xenograft mouse model was used to verify the tumorigenic effect of METTL16 in vivo. BALB/c nude mice (4 weeks old) were injected with METTL16 gene knock-down stable MGC803 GC cells (3 × 106 cells/mice, subcutaneous injection) or shNC control cells (3 × 106, subcutaneous injection), and the dose was 100 uL, with PBS as solvent. The tumour size was measured every 3-5 days. At the end of feeding (6 weeks after subcutaneous injection), the mice were killed and the tumours were extracted for histological analysis.
Response Summary METTL16-mediated m6A methylation promotes proliferation of gastric cancer cells through enhancing G1/S-specific cyclin-D1 (CCND1) expression.
Xenobiotics Compound(s) Regulating the m6A Methylation Regulator
Compound Name Butyrate Investigative
Synonyms
butyrate; butanoate; N-Butyrate; n-butanoate; Butanoic acid, ion(1-); propylformate; 461-55-2; butanate; 1-butanoate; propanecarboxylate; 1-butyrate; 1-propanecarboxylate; CHEMBL62381; NCGC00167555-01; ethyl,acetate; Sodium; butyrate; C11H23NOS; DTXSID8040432; CHEBI:17968; CH3-[CH2]2-COO(-); BDBM50079401; c0035; M135; AB01566831_01; Q55582441
    Click to Show/Hide
External link
Description
In cell model induced by sodium butyrate and cell density, while METTL3, METTL16 and WTAP were decreased during the differentiation of cells.
[4]
References
Ref 1 Gene Signatures and Prognostic Values of m6A Regulators in Hepatocellular Carcinoma. Front Genet. 2020 Oct 2;11:540186. doi: 10.3389/fgene.2020.540186. eCollection 2020.
Ref 2 PM2.5 induces pulmonary microvascular injury in COPD via METTL16-mediated m6A modification. Environ Pollut. 2022 Jun 15;303:119115. doi: 10.1016/j.envpol.2022.119115. Epub 2022 Mar 5.
Ref 3 METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer. J Cell Mol Med. 2021 Jul;25(14):6602-6617. doi: 10.1111/jcmm.16664. Epub 2021 Jun 2.
Ref 4 The differentiation of colorectal cancer is closely relevant to m6A modification. Biochem Biophys Res Commun. 2021 Mar 26;546:65-73. doi: 10.1016/j.bbrc.2021.02.001. Epub 2021 Feb 8.