본문 바로가기
KERD
논문KCI 등재

The Significance of N6-Methyladenosine RNA Methylation in Regulating the Hepatitis B Virus Life Cycle

Lee Wooseong|Moon Jae-Su|Cho Yong-Hee|Kim Yonghyo|Kim Geon-Woo
한국미생물·생명공학회 (The Korean Society For Microbiology And Biotechnology)|2024.02|Journal of Microbiology and Biotechnology|제34권 제2호|pp. 233-239|DOI 10.4014/jmb.2309.09013

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

innate immunityHepatitis B virushepatocellular carcinomaN6-methyladenosine RNA methylationHBV life cycleHBV chronic infection
주제분류생물학

초록

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferaselike (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6Amethylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

Abstract

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferaselike (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6Amethylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

참고문헌 (58)

  1. Seeger C, "Molecular biology of hepatitis B virus infection", Virology, 479-480, pp.672~686 (2015)
  2. Hu J, "Revisiting Hepatitis B Virus : challenges of curative therapies", J. Virol, 93, pp.e01032-19~ (2019)
  3. Yan H, "Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus", Elife, 1, pp.e00049~ (2012)
  4. Iwamoto M, "Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization", Proc. Natl. Acad. Sci. USA, 116, pp.8487~8492 (2019)
  5. Seeger C, "Hepatitis B virus biology", Microbiol. Mol. Biol. Rev, 64, pp.51~68 (2000)
  6. Roundtree IA, "Dynamic RNA modifications in gene expression regulation", Cell, 169, pp.1187~1200 (2017)
  7. Dominissini D, "Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq", Nature, 485, pp.201~206 (2012)
  8. Yue Y, "RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation", Genes Dev, 29, pp.1343~1355 (2015)
  9. Wang X, "Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex(vol 534, pg 575, 2016)", Nature, 542, pp.260~260 (2017)
  10. Fu Y, "FTO-mediated formation of N-6-hydroxymethyladenosine and N-6-formyladenosine in mammalian RNA", Nat. Commun, 4, pp.1798~ (2013)
  11. Zheng GQ, "ALKBH5 is a mammalian RNA demethylase that Impacts RNA metabolism and mouse fertility", Mol. Cell, 49, pp.18~29 (2013)
  12. Patil DP, "Reading m(6)A in the transcriptome : m(6)A-binding proteins", Trends Cell Biol, 28, pp.113~127 (2018)
  13. Shi HL, "YTHDF3 facilitates translation and decay of N6-methyladenosinemodified RNA", Cell Res, 27, pp.315~328 (2017)
  14. Wang X, "N-6-methyladenosine modulates messenger RNA translation efficiency", Cell, 161, pp.1388~1399 (2015)
  15. Du H, "YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex", Nat. Commun, 7, pp.12626~ (2016)
  16. Xiao W, "Nuclear m(6)A reader YTHDC1 regulates mRNA splicing", Mol. Cell, 61, pp.507~519 (2016)
  17. Kretschmer J, "The m(6)A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5'-3' exoribonuclease XRN1", RNA, 24, pp.1339~1350 (2018)
  18. Mao YH, "m(6)A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2", Nat. Commun, 10, pp.5332~ (2019)
  19. Kim GW, "The role of N6-methyladenosine modification in the life cycle and disease pathogenesis of hepatitis B and C viruses", Exp. Mol. Med, 53, pp.339~345 (2021)
  20. Imam H, "Epitranscriptomic(N6-methyladenosine)modification of viral RNA and virus-host interactions", Front. Cell. Infect. Microbiol, 10, pp.584283~ (2020)
  21. Gonzales-van Horn SR, "Making the Mark : The role of adenosine modifications in the life cycle of RNA viruses", Cell Host Microbe, 21, pp.661~669 (2017)
  22. Courtney DG, "Epitranscriptomic addition of m(5)C to HIV-1transcripts regulates viral gene expression", Cell Host Microbe, 26, pp.217~227 (2019)
  23. Gokhale NS, "N6-methyladenosine in flaviviridae viral RNA genomes regulates infection", Cell Host Microbe, 20, pp.654~665 (2016)
  24. Kennedy EM, "Posttranscriptional m(6)A editing of HIV-1mRNAs enhances viral gene expression", Cell Host Microbe, 19, pp.675~685 (2016)
  25. Tan B, "The RNA epitranscriptome of DNA viruses", J. Virol, 92, pp.e00696-18~ (2018)
  26. Kane SE, "Precise localization of m6A in Rous sarcoma virus RNA reveals clustering of methylation sites : implications for RNA processing", Mol. Cell. Biol, 5, pp.2298~2306 (1985)
  27. Hesser CR, "N6-methyladenosine modification and the YTHDF2 reader protein play cell type specific roles in lytic viral gene expression during Kaposi's sarcoma-associated herpesvirus infection", PLoS Pathog, 14, pp.e1006995~ (2018)
  28. Kim GW, "N6-methyladenine modification of hepatitis delta virus regulates its virion assembly by recruiting YTHDF1", J. Virol, 96, pp.e0112422~ (2022)
  29. Imam H, "N6-methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle", Proc. Natl. Acad. Sci. USA, 115, pp.8829~8834 (2018)
  30. Kim GW, "N6-methyladenosine modification of the 5' epsilon structure of the HBV pregenome RNA regulates its encapsidation by the viral core protein", Proc. Natl. Acad. Sci. USA, 119, pp.e2120485119~ (2022)
  31. Kim GW, "The RNA binding proteins YTHDC1 and FMRP regulate the nuclear export of N6-methyladenosine-modified Hepatitis B virus transcripts and affect the viral life cycle", J. Virol, 95, pp.e0009721~ (2021)
  32. Kim GW, "Hepatitis B virus X protein expression is tightly regulated by N6-methyladenosine modification of its mRNA", J. Virol, 96, pp.e0165521~ (2022)
  33. Imam H, "Interferon-stimulated gene 20(ISG20)selectively degrades N6-methyladenosine modified Hepatitis B Virus transcripts", PLoS Pathog, 16, pp.e1008338~ (2020)
  34. Kim GW, "Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral", host RNAs, 2021, pp.118, e201945118~
  35. Zheng YY, "Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice", Hepatology, 45, pp.16~21 (2007)
  36. Kariko K, "Suppression of RNA recognition by Toll-like receptors : the impact of nucleoside modification and the evolutionary origin of RNA", Immunity, 23, pp.165~175 (2005)
  37. Durbin AF, "RNAs Containing modified nucleotides fail to trigger RIG-I conformational changes for innate immune signaling", mBio, 7, pp.e00833-16~ (2016)
  38. Sioud M, "Suppression of immunostimulatory siRNA-driven innate immune activation by 2'-modified RNAs", Biochem. Biophys. Res. Commun, 361, pp.122~126 (2007)
  39. Uzri D, "Nucleotide sequences and modifications that determine RIG-I", RNA binding and signaling activities, 2009, pp.83, 4174~4184
  40. Takeuchi O, "Innate immunity to virus infection", Immunol. Rev, 227, pp.75~86 (2009)
  41. Schlee M, "Discriminating self from non-self in nucleic acid sensing", Nat. Rev. Immunol, 16, pp.566~580 (2016)
  42. Sato S, "The RNA sensor RIG-I dually functions as an innate sensor and direct antiviral factor for Hepatitis B virus", Immunity, 42, pp.123~132 (2015)
  43. Saito T, "Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA", Nature, 454, pp.523~527 (2008)
  44. Khan M, "Hepatitis B virus-induced Parkin-dependent recruitment of Linear Ubiquitin Assembly Complex(LUBAC)to mitochondria and attenuation of innate immunity", PLoS Pathog, 12, pp.e1005693~ (2016)
  45. Kim GW, "N6-Methyladenosine modification of hepatitis B and C viral RNAs attenuates host innate immunity via RIG-I signaling", J. Biol. Chem, 295, pp.13123~13133 (2020)
  46. Li N, "METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection", Cell Rep, 35, pp.109091~ (2021)
  47. Lu M, "N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I", Nat. Microbiol, 5, pp.584~598 (2020)
  48. Kim GW, "HBV-induced increased N6-methyladenosine modification of PTEN RNA affects innate immunity and contributes to HCC", Hepatology, 73, pp.533~547 (2020)
  49. Chen CY, "PTEN : Tumor suppressor and metabolic regulator", Front. Endocrinol. (Lausanne), 9, pp.338~ (2018)
  50. Li S, "The tumor suppressor PTEN has a critical role in antiviral innate immunity", Nat. Immunol, 17, pp.241~249 (2016)
  51. Zhao T, "N6-methyladenosine modification participates in the progression of Hepatitis B virus-related liver fibrosis by regulating immune cell infiltration", Front. Med. (Lausanne), 9, pp.821710~ (2022)
  52. Rao X, "N6-methyladenosine modification of circular RNA circ-ARL3 facilitates Hepatitis B virus-associated hepatocellular carcinoma via sponging miR-1305", IUBMB Life, 73, pp.408~417 (2021)
  53. Song MS, "The functions and regulation of the PTEN tumour suppressor", Nat. Rev. Mol. Cell Biol, 13, pp.283~296 (2012)
  54. Wang C, "Hepatitis B virus X(HBx)induces tumorigenicity of hepatic progenitor cells in 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine-treated HBx transgenic mice", Hepatology, 55, pp.108~120 (2012)
  55. Tirumuru N, "N(6)-methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression", Elife, 5, pp.e15528~ (2016)
  56. Lichinchi G, "Dynamics of human and viral RNA methylation during Zika virus infection", Cell Host Microbe, 20, pp.666~673 (2016)
  57. Guo G, "Advances in mRNA 5-methylcytosine modifications : Detection, effectors, biological functions, and clinical relevance", Mol. Ther. Nucleic Acids, 26, pp.575~593 (2021)
  58. Dimitrova DG, "RNA 2'-O-methylation(Nm)modification in human diseases", Genes(Basel), 10, pp.117~ (2019)

관련 논문AI추천

Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus이민종, Jun Sik Yoon, Sun Woong Kim, Yuri Cho대한간학회 · Clinical and Molecular Hepatology2022 · 제28권 제1호Biological roles of the RNA m6A modification and its implications in cancerHong Juyeong, Lee Ji Hoon, Xu Kexin생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Roles of RNA modifications in aging and age-related diseasesEunseok Kang, Hanseul Lee, Rosa Haque, Seung-Jae V. Lee생화학분자생물학회 · BMB Reports2025 · 제58권 제9호The roles of N6-methyladenosine and its target regulatory noncoding RNAs in tumors: classification, mechanisms, and potential therapeutic implicationsCheng Long, Gao Lei, Liu Ziying, Lv Gaoyuan, Sun Bei, Tang Qiushi, Wang Gang생화학분자생물학회 · Experimental and Molecular Medicine2023 · 제55권 Detection technologies for RNA modificationsLi Xiaoyu, Lu Liang, Zhang Yanling생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Deciphering the molecular mechanisms of epitranscriptome regulation in cancerJunho Choe, Seung Hun Han생화학분자생물학회 · BMB Reports2021 · 제54권 제2호

이 간행물의 다른 논문 (25건)

(E)-2-Methoxy-4-(3-(4-Methoxyphenyl) Prop-1-en-1-yl) Phenol Suppresses Breast Cancer Progression by Dual-Regulating VEGFR2 and PPARγKim Na-Yeon, 이희범, 홍진태, Park Hyo-Min, Yoon Do-Youngpp. 240-248Ganodermanontriol Suppresses the Progression of Lung Adenocarcinoma by Activating CES2 to Enhance the Metabolism of Mycophenolate MofetilWang Xin, Xie Qingfeng, Cao Zhuo, You Weiling, Cai Xiaoping, Shen Mei, Yin Zhangyong, Jiang Yiwei, Ye Siyupp. 249-261Anti-Inflammatory Activity of Vacuum Distillate from Panax ginseng Root on LPS-Induced RAW264.7 Cells박준성, 장영표, Lee Chanwoo, Lee Seulpp. 262-269LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose IntoleranceKim Myeong-Jin, Lee Min-Kyeong, Ryu Heeyeon, Lee Seungjun, Jeong Hyeon Hak, Lee Bonggipp. 270-279A Replication-Competent Retroviral Vector Expressing the HERV-W Envelope Glycoprotein is a Potential Tool for Cancer Gene Therapy정용태, Kang Byoung Kwonpp. 280-288
원문 보기