Biology Reference
In-Depth Information
Fig. 3 Model of the viral transcriptosome formed at the beginning of the infection. The input
genome that is deposited at the POD structure functions as the template for IE RNA synthesis.
Cellular hypophosphorylated RNAP IIa is recruited to the site along with cdk9 and cdk7, which
hyperphosphorylate RNAP IIa to the transcriptionally active RNAP IIo that serves as a platform
for RNA processing enzymes. The IE transcripts are synthesized and translated into the IE1-72
and IE2-86 proteins, which return to this nuclear body. IE1-72 causes POD dispersal and it also
disperses, while IE2-86 remains at the established transcription site, referred to as the transcripto-
some. The inset is an infected cell nucleus at 8 h p.i. and shows the accumulation of both cdk9 and
IE2 at several transcriptosomes
beginning of the infection serves as a specialized site for recruitment of cellular and
viral proteins necessary for viral transcription and replication. The correct phospho-
rylation of the RNAP II CTD at these sites is essential for accurate processing of
the IE transcripts and for transcription of early genes, and it appears that the
required level of phosphorylation is established within the first 8 h.
Perspectives
For more than a decade, we have known that HCMV dramatically alters cell cycle
regulatory pathways, leading to cell cycle arrest. These alterations begin as soon
as the viral particle enters the cell, but sustained effects require early viral gene
expression. The molecular mechanisms underlying the viral-mediated effects
operate at multiple levels, including altered RNA transcription, changes in the
levels and activity of cyclin-dependent kinases as well as other cellular kinases
involved in cell cycle control, modulation of protein stability through targeted
effects on the ubiquitin-proteasome degradation pathway, and movement of
Search WWH ::




Custom Search