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Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus

Mechanism of transcriptional regulation by the HMGA1–7SK–P-TEFbcomplex. A – HMGA1 can recruit P-TEFb/ 7SK snRNP complexto the paused transcription complex by interacting with DNA or a certaintranscription factor. B – the level of free HMGA1 in the nucleus isregulated by its binding to 7SK snRNP. Dissociation of HMGA1 from its complexwith 7SK snRNP can be caused by a factor that has not been identified yet[4, 72].
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Figure 8: Mechanism of transcriptional regulation by the HMGA1–7SK–P-TEFbcomplex. A – HMGA1 can recruit P-TEFb/ 7SK snRNP complexto the paused transcription complex by interacting with DNA or a certaintranscription factor. B – the level of free HMGA1 in the nucleus isregulated by its binding to 7SK snRNP. Dissociation of HMGA1 from its complexwith 7SK snRNP can be caused by a factor that has not been identified yet[4, 72].

Mentions: Another possible mechanism via which HMGA1 can be involved in transcriptionregulation has recently been proposed [71].It turns out that HMGA1 binds to loop 2 of RNA in 7SKsnNRP (7SK L2 RNA). As mentioned above, the key function of 7SK RNA is toregulate the level of the free P-TEFb factor activating transcriptionelongation [17]. This factor interactswith loop 1 and the HEXIM1 protein within 7SK snRNP. As a result, the HMGA1complex with 7SK snRNP and P-TEFb can be formed. The role of this complex intranscription regulation can be a dual one(Fig. 8)[72]. First, HMGA1 can bind directly to DNA ora transcription factor located on the promoter region and recruit P-TEFb to thepaused RNAP II elongation complex(Fig. 8A). Secondly,binding of 7SK to HMGA1 regulates the amount of free HMGA1 that can interactwith DNA and functions in various processes(Fig. 8B).The mechanism is believed to depend on the nature of the particular gene.


Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Mechanism of transcriptional regulation by the HMGA1–7SK–P-TEFbcomplex. A – HMGA1 can recruit P-TEFb/ 7SK snRNP complexto the paused transcription complex by interacting with DNA or a certaintranscription factor. B – the level of free HMGA1 in the nucleus isregulated by its binding to 7SK snRNP. Dissociation of HMGA1 from its complexwith 7SK snRNP can be caused by a factor that has not been identified yet[4, 72].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837570&req=5

Figure 8: Mechanism of transcriptional regulation by the HMGA1–7SK–P-TEFbcomplex. A – HMGA1 can recruit P-TEFb/ 7SK snRNP complexto the paused transcription complex by interacting with DNA or a certaintranscription factor. B – the level of free HMGA1 in the nucleus isregulated by its binding to 7SK snRNP. Dissociation of HMGA1 from its complexwith 7SK snRNP can be caused by a factor that has not been identified yet[4, 72].
Mentions: Another possible mechanism via which HMGA1 can be involved in transcriptionregulation has recently been proposed [71].It turns out that HMGA1 binds to loop 2 of RNA in 7SKsnNRP (7SK L2 RNA). As mentioned above, the key function of 7SK RNA is toregulate the level of the free P-TEFb factor activating transcriptionelongation [17]. This factor interactswith loop 1 and the HEXIM1 protein within 7SK snRNP. As a result, the HMGA1complex with 7SK snRNP and P-TEFb can be formed. The role of this complex intranscription regulation can be a dual one(Fig. 8)[72]. First, HMGA1 can bind directly to DNA ora transcription factor located on the promoter region and recruit P-TEFb to thepaused RNAP II elongation complex(Fig. 8A). Secondly,binding of 7SK to HMGA1 regulates the amount of free HMGA1 that can interactwith DNA and functions in various processes(Fig. 8B).The mechanism is believed to depend on the nature of the particular gene.

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus