Transcription regulation of African swine fever virus: dual role of M1249L
Abstract African swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase (vRNAP), temporally expressed transcription factors and transcript associated proteins, facili...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54461-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849221103466053632 |
|---|---|
| author | Dongming Zhao Nan Wang Xiaoying Feng Zhenjiang Zhang Kongen Xu Tao Zheng Yunge Yang Xuemei Li Xianjin Ou Rui Zhao Zihe Rao Zhigao Bu Yutao Chen Xiangxi Wang |
| author_facet | Dongming Zhao Nan Wang Xiaoying Feng Zhenjiang Zhang Kongen Xu Tao Zheng Yunge Yang Xuemei Li Xianjin Ou Rui Zhao Zihe Rao Zhigao Bu Yutao Chen Xiangxi Wang |
| author_sort | Dongming Zhao |
| collection | DOAJ |
| description | Abstract African swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase (vRNAP), temporally expressed transcription factors and transcript associated proteins, facilitating cross-species transmission via intermediate host. The protein composition of the virion and the presence of transcription factors in virus genome suggest existence of distinct transcription systems during viral infection. However, the precise mechanisms of transcription regulation remain elusive. Through analyses of dynamic transcriptome, vRNAP-associated components and cell-based assay, the critical role of M1249L in viral transcription regulation has been highlighted. Atomic-resolution structures of vRNAP-M1249L supercomplex, exhibiting a variety of conformations, have uncovered the dual functions of M1249L. During early transcription, M1249L could serve as multiple temporary transcription factors with C-terminal domain acting as a switcher for activation/inactivation, while during late transcription it aids in the packaging of the transcription machinery. The structural and functional characteristics of M1249L underscore its vital roles in ASFV transcription, packaging, and capsid assembly, presenting novel opportunities for therapeutic intervention. |
| format | Article |
| id | doaj-art-b897bb29a9894c7e9c58c1ce0ba292d7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b897bb29a9894c7e9c58c1ce0ba292d72024-11-24T12:33:49ZengNature PortfolioNature Communications2041-17232024-11-0115111410.1038/s41467-024-54461-1Transcription regulation of African swine fever virus: dual role of M1249LDongming Zhao0Nan Wang1Xiaoying Feng2Zhenjiang Zhang3Kongen Xu4Tao Zheng5Yunge Yang6Xuemei Li7Xianjin Ou8Rui Zhao9Zihe Rao10Zhigao Bu11Yutao Chen12Xiangxi Wang13State Key Laboratory for Animal Disease Control and Prevention, National African Swine Fever Para-reference Laboratory, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesState Key Laboratory for Animal Disease Control and Prevention, National African Swine Fever Para-reference Laboratory, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesState Key Laboratory for Animal Disease Control and Prevention, National African Swine Fever Para-reference Laboratory, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesState Key Laboratory for Animal Disease Control and Prevention, National African Swine Fever Para-reference Laboratory, National High Containment Facilities for Animal Diseases Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesNational Laboratory of Biomacromolecules, Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of SciencesAbstract African swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase (vRNAP), temporally expressed transcription factors and transcript associated proteins, facilitating cross-species transmission via intermediate host. The protein composition of the virion and the presence of transcription factors in virus genome suggest existence of distinct transcription systems during viral infection. However, the precise mechanisms of transcription regulation remain elusive. Through analyses of dynamic transcriptome, vRNAP-associated components and cell-based assay, the critical role of M1249L in viral transcription regulation has been highlighted. Atomic-resolution structures of vRNAP-M1249L supercomplex, exhibiting a variety of conformations, have uncovered the dual functions of M1249L. During early transcription, M1249L could serve as multiple temporary transcription factors with C-terminal domain acting as a switcher for activation/inactivation, while during late transcription it aids in the packaging of the transcription machinery. The structural and functional characteristics of M1249L underscore its vital roles in ASFV transcription, packaging, and capsid assembly, presenting novel opportunities for therapeutic intervention.https://doi.org/10.1038/s41467-024-54461-1 |
| spellingShingle | Dongming Zhao Nan Wang Xiaoying Feng Zhenjiang Zhang Kongen Xu Tao Zheng Yunge Yang Xuemei Li Xianjin Ou Rui Zhao Zihe Rao Zhigao Bu Yutao Chen Xiangxi Wang Transcription regulation of African swine fever virus: dual role of M1249L Nature Communications |
| title | Transcription regulation of African swine fever virus: dual role of M1249L |
| title_full | Transcription regulation of African swine fever virus: dual role of M1249L |
| title_fullStr | Transcription regulation of African swine fever virus: dual role of M1249L |
| title_full_unstemmed | Transcription regulation of African swine fever virus: dual role of M1249L |
| title_short | Transcription regulation of African swine fever virus: dual role of M1249L |
| title_sort | transcription regulation of african swine fever virus dual role of m1249l |
| url | https://doi.org/10.1038/s41467-024-54461-1 |
| work_keys_str_mv | AT dongmingzhao transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT nanwang transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT xiaoyingfeng transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT zhenjiangzhang transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT kongenxu transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT taozheng transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT yungeyang transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT xuemeili transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT xianjinou transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT ruizhao transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT ziherao transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT zhigaobu transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT yutaochen transcriptionregulationofafricanswinefevervirusdualroleofm1249l AT xiangxiwang transcriptionregulationofafricanswinefevervirusdualroleofm1249l |