In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-03-05)
Abstract:
The rates at which many genes are expressed as proteins are limited by the efficiency of a process called transcriptional elongation. This process takes place as the stretch of DNA that defines the gene is transcribed into an RNA molecule and it is catalyzed by an enzyme called RNA polymerase II. However, this enzyme can become trapped, and another enzyme called P-TEFb (positive transcription elongation factor b) is needed to release it. P-TEFb and other elongation factors therefore have an important role in gene expression. The human immunodeficiency virus (HIV) is a retrovirus that hijacks the gene expression processes in human immune cells to replicate the RNA genome of the virus. To do this, the virus produces a protein called Tat that recruits P-TEFb as part of a multi-protein machine called the super elongation complex. This ensures that the process of transcriptional elongation, and hence the overall replication process, is highly efficient. There are gaps, however, in our knowledge of the architecture of the super elongation complex, which is known to be organized on a flexible scaffold. In turn, the molecular basis for the interaction between HIV-1 Tat and P-TEFb within the super elongation complex is not well understood. Now Schulze-Gahmen et al. show that only one of the two subunits in P-TEFb—a cyclin known as CycT1—binds to the AFF4 scaffold protein in the super elongation complex. In addition to assisting with the expression of hundreds of human genes, super elongation complexes containing P-TEFb-AFF4 are hijacked in various forms of cancer and viral infections, including HIV/AIDS. Schulze-Gahmen et al. show that AFF4 can directly contact HIV-1 Tat, which binds to the P-TEFb-AFF4 complex much more strongly than it binds to P-TEFb alone. This suggests that HIV-1 Tat evolved to work within the super elongation complex. Moreover, Schulze-Gahmen et al. reveal that HIV-1 Tat binds to a cleft between the P-TEFb enzyme and the AFF4 protein, which raises the possibility that this cleft could be used as a target for anti-HIV/AIDS drugs.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.00327.001
DOI:
10.7554/eLife.00327.002
DOI:
10.7554/eLife.00327.003
DOI:
10.7554/eLife.00327.004
DOI:
10.7554/eLife.00327.005
DOI:
10.7554/eLife.00327.006
DOI:
10.7554/eLife.00327.007
DOI:
10.7554/eLife.00327.008
DOI:
10.7554/eLife.00327.009
DOI:
10.7554/eLife.00327.010
DOI:
10.7554/eLife.00327.011
DOI:
10.7554/eLife.00327.012
DOI:
10.7554/eLife.00327.013
DOI:
10.7554/eLife.00327.014
DOI:
10.7554/eLife.00327.015
DOI:
10.7554/eLife.00327.016
DOI:
10.7554/eLife.00327.017
DOI:
10.7554/eLife.00327.018
DOI:
10.7554/eLife.00327.019
DOI:
10.7554/eLife.00327.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3
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