Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax
Abstract The mouse mammary tumor virus (MMTV) encodes a 5’ element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5’ element is Rem-responsive or has any functional interaction with host/viral...
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| Format: | Article |
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Nature Portfolio
2024-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07139-9 |
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| author | Thanumol Abdul Khader Waqar Ahmad Shaima Akhlaq Neena Gopinathan Panicker Bushra Gull Jasmin Baby Tahir A. Rizvi Farah Mustafa |
| author_facet | Thanumol Abdul Khader Waqar Ahmad Shaima Akhlaq Neena Gopinathan Panicker Bushra Gull Jasmin Baby Tahir A. Rizvi Farah Mustafa |
| author_sort | Thanumol Abdul Khader |
| collection | DOAJ |
| description | Abstract The mouse mammary tumor virus (MMTV) encodes a 5’ element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5’ element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5’ element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5’ element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first betaretrovirus to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy. |
| format | Article |
| id | doaj-art-4cf5ca87ffbb4b14890d839fc9bef86f |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-4cf5ca87ffbb4b14890d839fc9bef86f2024-11-17T12:42:53ZengNature PortfolioCommunications Biology2399-36422024-11-017111410.1038/s42003-024-07139-9Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and TaxThanumol Abdul Khader0Waqar Ahmad1Shaima Akhlaq2Neena Gopinathan Panicker3Bushra Gull4Jasmin Baby5Tahir A. Rizvi6Farah Mustafa7Department of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityDepartment of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityDepartment of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityDepartment of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityDepartment of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityDepartment of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityASPIRE Research Institute in Precision MedicineDepartment of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) UniversityAbstract The mouse mammary tumor virus (MMTV) encodes a 5’ element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5’ element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5’ element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5’ element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first betaretrovirus to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy.https://doi.org/10.1038/s42003-024-07139-9 |
| spellingShingle | Thanumol Abdul Khader Waqar Ahmad Shaima Akhlaq Neena Gopinathan Panicker Bushra Gull Jasmin Baby Tahir A. Rizvi Farah Mustafa Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax Communications Biology |
| title | Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax |
| title_full | Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax |
| title_fullStr | Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax |
| title_full_unstemmed | Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax |
| title_short | Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax |
| title_sort | transactivation of the novel 5 cis acting element of mouse mammary tumor virus mmtv by human retroviral transactivators tat and tax |
| url | https://doi.org/10.1038/s42003-024-07139-9 |
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