Inhibition of HIV-1 Transcription and Replication by a Newly Identified Cyclin T1 Splice Variant

Gao, Guozhen; Wu, Xiaoyun; Zhou, Jieqiong; He, Miao; He, Johnny J.; Guo, Deyin

doi:10.1074/jbc.m112.438465

Cited by 9 publications

(19 citation statements)

References 74 publications

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“…Two Cyclin T1 splice variants, namely CycT1a and CycT1b, were reported and play contrary roles in transcription elongation [Gao et al, 2013].The ratio of CycT1b and CycT1a in the cells might be a mark of general transcription activation or suppression. CycT1b is generated by exon skipping of its exon 7, and thus could be specifically amplified by the primer targeting the exon junction of exon 6 and 8 ( CycT1b by semi-quantitative RT-PCR (Fig.…”

Section: Results: Screening For Splicing Factors Targeting the Gene Fmentioning

confidence: 99%

“…On the other hand, the role of CycT1b in the regulation of gene transcription remains to be elucidated. Data from our previous work suggested that CycT1b might negatively regulate the transcription of certain cellular genes [Gao et al, 2013].…”

Section: Cyct1-dependent Cellular Genesmentioning

confidence: 96%

“…c-Myc, CAD, JunB, HSP70 and CMV promoters were amplified by PCR amplifying their promoter regions plus the downstream 100 nucleotides from human 293T genomic DNA, as described previously [Eberhardy and Farnham, 2002;Jajarmi et al, 2013;Mathas et al, 2002;Mognol et al, 2012].Then the promoter sequences were inserted into pGL3 basic vector to construct pGL3-c-Myc, pGL3-CAD, pGL3-JunB, and pGL3-hsp70 luciferase reporter plasmids respectively.CycT1a and CycT1b constructs, IFN-β promoter plasmids and pRL-TK plasmid were previously described [Gao et al, 2013;Zhong et al, 2008].…”

Section: Plasmid Construction and Mutagenesismentioning

confidence: 99%

“…Human CycT1b was reported to inhibit HIV-1 replication on the transcription level, while CycT1a was shown as a key factor to support HIV-1 transcription elongation [Gao et al, 2013;Wei et al, 1998]. …”

Section: Asf/sf2 Reversely Correlates With Tat-mediated Hiv-1 Ltr Tramentioning

confidence: 99%

“…Cyclin T1 has been recently found to express into two splice variants, the conventional form CycT1a and the new variant CycT1b, through the alternative splicing at its exon 7 [Gao et al, 2013;Urano et al, 2012].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine‐Arginine‐Rich Protein ASF/SF2

Zhou

Gao

Hou

et al. 2017

J of Cellular Biochemistry

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Positive transcription elongation factor-b (P-TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for efficient proceeding to the transcription elongation. It consists of two core subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is the major and most studied combination. We have previously identified a novel splice variant of cyclin T1, cyclin T1b, which negatively regulates the transcription elongation of HIV-1 genes as well as several host genes. In this study, we revealed the serine-arginine-rich protein, ASF/SF2, as a regulatory factor of the alternative splicing of cyclin T1 gene. ASF/SF2 promotes the production of cyclin T1b versus cyclin T1a and regulates the expression of cyclin T1-depedent genes at the transcription level. We further found that a cis-element on exon 8 is responsible for the skipping of exon 7 mediated by ASF/SF2. Collectively, ASF/SF2 is identified as a splicing regulator of cyclin T1, which contributes to the control of the subsequent transcription events. J. Cell. Biochem. 118: 4020-4032, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Results: Screening For Splicing Factors Targeting the Gene Fmentioning

confidence: 99%

Section: Cyct1-dependent Cellular Genesmentioning

confidence: 96%

Section: Plasmid Construction and Mutagenesismentioning

confidence: 99%

Section: Asf/sf2 Reversely Correlates With Tat-mediated Hiv-1 Ltr Tramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine‐Arginine‐Rich Protein ASF/SF2

Zhou

Gao

Hou

et al. 2017

J of Cellular Biochemistry

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Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection

Hou

Chen

Wang

et al. 2015

Sci Rep

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193

175

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Genome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4+ cells by binding to envelope protein, gp120. Here, we show that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to HIV-1 resistance of human primary CD4+ T cells. We also show that the Cas9-mediated ablation of CXCR4 demonstrated high specificity and negligible off-target effects without affecting cell division and propagation. The precise and efficient genome editing of CXCR4 will provide a new strategy for therapeutic application against HIV-1 infection.

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Short Communication: Long Noncoding RNA GAS5 Inhibits HIV-1 Replication Through Interaction with miR-873

Chen

Zuo

et al. 2018

AIDS Research and Human Retroviruses

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HIV is the causative pathogen of AIDS, which has generated worldwide concern. Long noncoding RNAs (lncRNAs) are a rising star in virus-host cross-talk pathways; they are differentially expressed during many viral infections and are involved in multiple biological processes. Currently, lncRNA growth arrest-specific transcript 5 (GAS5) is known to be downregulated during HIV-1 infection. However, the functions and mechanisms of GAS5 in HIV-1 infection remain largely unknown. In this report, it was found for the first time that GAS5 could inhibit HIV-1 replication. Interestingly, using bioinformatics analyses (with Genomica and starBase.v2.0), GAS5 was found to potentially interact with miR-873. It was further verified that GAS5 could suppress miR-873. Moreover, miR-873 could promote HIV-1 replication. Together, these results not only suggest that GAS5 may inhibit HIV-1 replication through interaction with miR-873 but the results may also provide novel biomarkers for antiviral drugs or potential targets for future therapeutics for HIV/AIDS.

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Inhibition of HIV-1 Transcription and Replication by a Newly Identified Cyclin T1 Splice Variant

Cited by 9 publications

References 74 publications

Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine‐Arginine‐Rich Protein ASF/SF2

Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine‐Arginine‐Rich Protein ASF/SF2

Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection

Short Communication: Long Noncoding RNA GAS5 Inhibits HIV-1 Replication Through Interaction with miR-873

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