# Potential roles of N6-methyladenosine (m6A) in immune cells **Authors:** Chang Liu, Zhe Yang, Rong Li, Yanju Wu, Ming Chi, Shuting Gao, Xun Sun, Xin Meng, Biao Wang PMC · DOI: 10.1186/s12967-021-02918-y · Journal of Translational Medicine · 2021-06-08 ## TL;DR This review explores how m6A RNA modification influences immune cell function and immune responses, highlighting its role in disease development and potential therapeutic applications. ## Contribution The paper provides a comprehensive overview of m6A's role in immunoregulatory networks and its impact on immune responses. ## Key findings - m6A modification is a key post-transcriptional regulator of immune responses in cells. - Deregulation of m6A is linked to various human diseases and immune system dysfunctions. - The review identifies m6A regulators and their influence on immunoregulatory networks. ## Abstract N6-methyl-adenosine (m6A) is one of the most common internal modifications on RNA molecules present in mammalian cells. Deregulation of m6A modification has been recently implicated in many types of human diseases. Therefore, m6A modification has become a research hotspot for its potential therapeutic applications in the treatment of various diseases. The immune system mostly involves different types of immune cells to provide the first line of defense against infections. The immunoregulatory network that orchestrate the immune responses to new pathogens plays a pivotal role in the development of the disease. And m6A modification has been demonstrated to be a major post-transcriptional regulator of immune responses in cells. In this review, we summarize the participants involved in m6A regulation and try to reveal how m6A modification affects the immune responses via changing the immunoregulatory networks. ## Full-text entities - **Genes:** Ddit3 (DNA-damage inducible transcript 3) [NCBI Gene 13198] {aka AltDDIT3, CHOP-10, CHOP10, chop, gadd153}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Traf3 (TNF receptor-associated factor 3) [NCBI Gene 22031] {aka CAP-1, CD40bp, CRAF1, LAP1, T-BAM, TRAFAMN}, FTO (FTO alpha-ketoglutarate dependent dioxygenase) [NCBI Gene 79068] {aka ALKBH9, BMIQ14, GDFD, IFEX9}, ZC3H13 (zinc finger CCCH-type containing 13) [NCBI Gene 23091] {aka KIAA0853, Xio}, CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236] {aka BLR2, CC-CKR-7, CCR-7, CD197, CDw197, CMKBR7}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, SOX10 (SRY-box transcription factor 10) [NCBI Gene 6663] {aka DOM, PCWH, SOX-10, WS2E, WS4, WS4C}, Spi1 (Spi-1 proto-oncogene) [NCBI Gene 20375] {aka Dis-1, Dis1, PU.1, Sfpi-1, Sfpi1, Spi-1}, Alkbh5 (alkB homolog 5, RNA demethylase) [NCBI Gene 268420] {aka Abh5, E130207K11, Ofoxd}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, Srsf10 (serine and arginine-rich splicing factor 10) [NCBI Gene 14105] {aka FUSIP2, Fusip1, NSSR1, NSSR2, Nssr, SRrp40}, Tal1 (T cell acute lymphocytic leukemia 1) [NCBI Gene 21349] {aka Hpt, SCL/tal-1, Scl, bHLHa17, tal-1}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, Bmi1 (Bmi1 proto-oncogene, polycomb ring finger) [NCBI Gene 12151] {aka Bmi-1, Pcgf4}, SERPINF1 (serpin family F member 1) [NCBI Gene 5176] {aka EPC-1, OI12, OI6, PEDF, PIG35}, Tceal1 (transcription elongation factor A (SII)-like 1) [NCBI Gene 237052] {aka 0610011M09Rik, P21, SIIR, pp21}, EIF3A (eukaryotic translation initiation factor 3 subunit A) [NCBI Gene 8661] {aka EIF3, EIF3S10, P167, TIF32, eIF3-p170, eIF3-theta}, Xist (inactive X specific transcripts) [NCBI Gene 213742] {aka A430022B11}, ZMYM1 (zinc finger MYM-type containing 1) [NCBI Gene 79830] {aka MYM}, Ddx46 (DEAD box helicase 46) [NCBI Gene 212880] {aka 2200005K02Rik, 8430438J23Rik, mKIAA0801}, PRDM1 (PR/SET domain 1) [NCBI Gene 639] {aka BLIMP-1, BLIMP1, PRDI-BF1}, Igf2bp1 (insulin-like growth factor 2 mRNA binding protein 1) [NCBI Gene 140486] {aka CRD-BP, Crdbp, D030026A21Rik, D11Moh40e, D11Moh45, IMP1}, Ythdf1 (YTH N6-methyladenosine RNA binding protein 1) [NCBI Gene 228994] {aka 2210410K23Rik, 8030473O16}, TIRAP (TIR domain containing adaptor protein) [NCBI Gene 114609] {aka BACTS1, Mal, MyD88-2, wyatt}, Hnrnpa2b1 (heterogeneous nuclear ribonucleoprotein A2/B1) [NCBI Gene 53379] {aka 9130414A06Rik, Hnrpa2, Hnrpa2b1, hnrnp-A}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, Elavl1 (ELAV like RNA binding protein 1) [NCBI Gene 15568] {aka 2410055N02Rik, HUR, Hua}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, IGF2BP2 (insulin like growth factor 2 mRNA binding protein 2) [NCBI Gene 10644] {aka IMP-2, IMP2, VICKZ2}, Fmr1 (fragile X messenger ribonucleoprotein 1) [NCBI Gene 14265] {aka FMRP, Fmr-1}, Stat1 (signal transducer and activator of transcription 1) [NCBI Gene 20846] {aka 2010005J02Rik}, Ythdc1 (YTH domain containing 1) [NCBI Gene 231386] {aka A730098D12Rik, mKIAA1966}, MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4) [NCBI Gene 9448] {aka FLH21957, HEL-S-31, HGK, MEKKK4, NIK}, CNOT1 (CCR4-NOT transcription complex subunit 1) [NCBI Gene 23019] {aka AD-005, CDC39, HPE12, NOT1, NOT1H, VIBOS}, Matr3 (matrin 3) [NCBI Gene 17184] {aka 1110061A14Rik, 2810017I02Rik, D030046F20Rik, mKIAA0723}, Rbm15 (RNA binding motif protein 15) [NCBI Gene 229700] {aka C230088J01Rik, mKIAA1438}, NR4A2 (nuclear receptor subfamily 4 group A member 2) [NCBI Gene 4929] {aka HZF-3, IDLDP, NOT, NURR1, RNR1, TINUR}, Ythdf2 (YTH N6-methyladenosine RNA binding protein 2) [NCBI Gene 213541] {aka 9430020E02Rik, HGRG8, NY-REN-2}, mettl3 (methyltransferase like 3) [NCBI Gene 100004398] {aka MT-A70, fj82g07, wu:fj82g07, zgc:77093}, RBM15 (RNA binding motif protein 15) [NCBI Gene 64783] {aka OTT, OTT1}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, YTHDF1 (YTH N6-methyladenosine RNA binding protein F1) [NCBI Gene 54915] {aka C20orf21, DF1}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, BMI1 (BMI1 proto-oncogene, polycomb ring finger) [NCBI Gene 648] {aka FLVI2/BMI1, PCGF4, RNF51, flvi-2/bmi-1}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Ythdc2 (YTH domain containing 2) [NCBI Gene 240255] {aka 3010002F02Rik, mYTHDC2}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, ARID3A (AT-rich interaction domain 3A) [NCBI Gene 1820] {aka BRIGHT, DRIL1, DRIL3, E2FBP1}, Mettl14 (methyltransferase 14, N6-adenosine-methyltransferase subunit) [NCBI Gene 210529] {aka G430022H21Rik, mKIAA1627}, Igf2 (insulin-like growth factor 2) [NCBI Gene 16002] {aka Igf-2, Igf-II, M6pr, Mpr, Peg2}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, Srsf3 (serine and arginine-rich splicing factor 3) [NCBI Gene 20383] {aka Sfrs3, X16}, METTL16 (methyltransferase 16, RNA N6-adenosine) [NCBI Gene 79066] {aka METT10D}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta} - **Diseases:** B cell lymphoma (MESH:D016393), melanoma (MESH:D008545), DLBCL (MESH:D016403), inflammation (MESH:D007249), gastric cancer (MESH:D013274), necrotic tissue (MESH:D017695), colon cancer (MESH:D015179), leukemia (MESH:D007938), autoimmunity (MESH:D001327), MTC (MESH:C536512), age-related diseases (MESH:D010024), degenerative diseases (MESH:D019636), metastasis (MESH:D009362), infection (MESH:D007239), tumorigenesis (MESH:D063646), hematopoietic malignancies (MESH:D019337), non-small cell lung cancer (MESH:D002289), viral infection (MESH:D014777), cancer (MESH:D009369), prostate cancer (MESH:D011471), lung cancer (MESH:D008175), hematological disorders (MESH:D006402), reproductive system diseases (MESH:D060737), Alzheimer's disease (MESH:D000544), diabetes (MESH:D003920), mantle cell lymphoma (MESH:D020522), HCC (MESH:D006528), breast cancer (MESH:D001943), AML (MESH:D015470) - **Chemicals:** 2-hydroxyglutaric acid (MESH:C019417), m(6)A (MESH:C005955), LPS (MESH:D008070), Asp-Pro-Pro-Trp (-), S-adenosylmethionine (MESH:D012436), N6-methyl-adenosine (MESH:C010223), (MESH:D000241) - **Species:** Human gammaherpesvirus 8 (no rank) [taxon 37296], Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Drosophila melanogaster (fruit fly, species) [taxon 7227], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Human immunodeficiency virus 1 (no rank) [taxon 11676] - **Cell lines:** MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), XS — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AV87), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC8186046/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8186046/full.md ## References 106 references — full list in the complete paper: https://tomesphere.com/paper/PMC8186046/full.md --- Source: https://tomesphere.com/paper/PMC8186046