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新型小鼠乳腺肿瘤病毒(MMTV)5'顺式作用元件的人逆转录病毒转录激活子 Tat 和 Tax 的转录激活。

Transactivation of the novel 5' cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax.

机构信息

Department of Biochemistry and Molecular Biology, College of Medicine & Health Sciences (CMHS), United Arab Emirates (UAE) University, Al Ain, UAE.

ASPIRE Research Institute in Precision Medicine, Abu Dhabi, UAE.

出版信息

Commun Biol. 2024 Nov 16;7(1):1521. doi: 10.1038/s42003-024-07139-9.

DOI:10.1038/s42003-024-07139-9
PMID:39550519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11569226/
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.

摘要

鼠乳腺肿瘤病毒(MMTV)编码 5' 元件,该元件对于其基因组的转录至关重要,同时还编码 Rem/Rem 反应元件(RmRE),负责该未剪接 RNA 的核输出。本研究旨在测试 5' 元件是否对 Rem 有反应,或者与宿主/病毒因子是否有任何功能相互作用,以促进 MMTV 基因表达。我们的结果表明,5' 元件对 Rem 无反应,但可被 HIV Tat 和 HTLV-1 Tax 激活剂反式激活。反过来,MMTV 不仅可以反式激活 HIV TAR(类似于 HTLV Tax),还可以反式激活其 5' 元件。此外,我们揭示了 pTEFb 的参与,pTEFb 是一种与 Tat/Tax 反式激活相关的通用延伸因子。这使得 MMTV 成为第一个编码 Rem/RRE 和 Tat/Tax/TRE 样转录调控系统的β逆转录病毒。本研究不仅应增强我们对逆转录病毒复制和病毒诱导的癌症/免疫缺陷综合征的理解,而且还应促进用于人类基因治疗的改良逆转录病毒载体的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/6e5331a80e1b/42003_2024_7139_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/9def9e719262/42003_2024_7139_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/79fc2b10443d/42003_2024_7139_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/07a3d82634cd/42003_2024_7139_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/04eeef1856ad/42003_2024_7139_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/b3400cf5f6c6/42003_2024_7139_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/71bc6d6c818b/42003_2024_7139_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/dbc4c2ad06e3/42003_2024_7139_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/6e5331a80e1b/42003_2024_7139_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/9def9e719262/42003_2024_7139_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/79fc2b10443d/42003_2024_7139_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/07a3d82634cd/42003_2024_7139_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/04eeef1856ad/42003_2024_7139_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/b3400cf5f6c6/42003_2024_7139_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/71bc6d6c818b/42003_2024_7139_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/dbc4c2ad06e3/42003_2024_7139_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f31/11569226/6e5331a80e1b/42003_2024_7139_Fig8_HTML.jpg

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