# The Emerging Roles of RNA Modifications in Glioblastoma
## 3 RNA Modifications in GBM
### RNA m\({}^{6}\)A Modification in GBM  
RNA m\({}^{6}\)A modification is the most prevalent and abundant modifications that occur in the mRNAs, rRNAs and small nuclear RNAs (snRNAs) [35]. m\({}^{6}\)A modification of mRNA usually occurs in nuclear speckles where the methyltransferases and demethylases are concentrated [29] and are enriched in single nucleotide polymorphisms (SNPs) [36]. Generally, the enzymatic core METTLE3 and methyltransferase like 14 (METTL14), as well as Wilms' tumor 1-associated protein (WTAP), Virillizer like m6A methyltransferase associated protein (VIRMA/KIAA1429), RNA-binding motif protein 15 (RBM15), RNA-binding motif protein 15B (RBM15B/OTT3), zinc finger CCCH domain-containing protein 13 (ZC3H13, as known as Flacc and KIAA0853) and Hakai (also known as Cbl proto-oncogene like 1, CBLL1) constitute of a methyltransferase complex, also known as m\({}^{6}\)A-METTL associated complex (MACOM), that can mediates the m\({}^{6}\)A methylation. Meanwhile, two demethylases, Fat mass and obesity-associated protein (FTO) and ALKBH5, catalyze the m\({}^{6}\)A demethylation [37; 38; 39; 40; 41; 42]. Several m\({}^{6}\)A-binding proteins such as YTH N\({}^{6}\)-methyladenosine RNA binding protein 1/2/3 (YTHDF1/2/3) and YTH domain-containing 1/2/3 (YTHDC1/2/3), which have the YTH domain, are readers that mediate the degradation of m\({}^{6}\)A-labelled RNAs [43; 44]. Other factors, such as insulin-like growth factor 2 mRNA-binding protein 1/2/3 (IGF2 BP1/2/3, also known as IMP1/2/3), eukaryotic translation initiation factor 3a/b/h (eIF3a/b/h), heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) and heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) were recently shown to be able to read the m\({}^{6}\)A marks, too [22]. These m\({}^{6}\)A reader proteins can recognize these marks and also can play key roles in the RNA stabilization of the writers [45]. m\({}^{6}\)A marks recognized by different readers with different sub-locations may exert different functions: the readers in the nucleus, such as hnRNPC, hnRNPA2B1 and YTHDC1, are responsible for RNA structure switching, alternative splicing, microRNA maturation, RNA stability, RNA export and X chromosome inactivation; while readers in the cytoplasm, such as YTHDF1/2/3 and YTHDC2, are mainly responsible for mRNA translation and decay [46]. As RNA m\({}^{6}\)A affects RNA stability, processing, splicing, translation, and the epigenetic function of some non-coding RNAs (ncRNAs) [47; 48], it plays essential role in cell fate determination, embryonic stem cell maintenance and specification, T-cell homeostasis, neuronal functions, sex determination as well as pathogenesis [49; 50; 51; 52; 53; 54]. In tumors, m\({}^{6}\)A also emerges as an important modulator. For instance, METTL3 drives tumorigenicity and metastasis through suppressing suppressor of cytokine signaling 2 (SOCS2) expression in hepatocellular carcinoma [55]. \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Gene Symbol** & **Gene Description** & \ \begin{tabular}{c} **Role in RNA** \\ **Modification** \\ \end{tabular}  & **Expression** & **Biological Function** & **Mechanism** & **Reference** \\ \hline \multirow{6}{*}{METTL3} & \multirow{6}{*}{Methyltransferase- like 3} & & & &
\begin{tabular}{c} Installs m\({}^{\text{\text{\text{\text{\text{\text{\textasci