Linked Life Data

15937951

Source:http://linkedlifedata.com/resource/pubmed/id/15937951

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-8-30
pubmed:abstractText
Human immunodeficiency virus type-1 (HIV-1) relies on both partial and complete splicing of its full-length RNA transcripts to generate a distribution of essential spliced mRNA products. The complexity of the splicing process, which can employ multiple alternative splice sites, challenges our ability to understand how mutations in splice sites may influence the composition of the resulting mRNA pool and, more broadly, the development of viral progeny. Here, we begin to systematically address these issues by developing a mechanistic mathematical model for the splicing process. We identify as key parameters the probabilities that the cellular splice machinery selects specific splice acceptors, and we show how the splicing process depends on these probabilities. Further, by incorporating this splicing model into a detailed kinetic model for HIV-1 intracellular development we find that an increase in the fraction of either rev or tat mRNA in the HIV-1 mRNA pool is generally beneficial for HIV-1 growth. However, a splice site mutation that excessively increases the fraction of either mRNA can be detrimental due to the corresponding reduction in the other mRNA, suggesting that a balance of Rev and Tat is needed in order for HIV-1 to optimize its growth. Although our model is based on still very limited quantitative data on RNA splicing, Rev-mediated splicing regulation and nuclear export, and the effects of associated mutations, it serves as a starting point for better understanding how variations in essential post-transcriptional functions can impact the intracellular development of HIV-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3592
pubmed:author
pubmed:copyrightInfo
Copyright 2005 Wiley Periodicals, Inc
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
877-93
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
In silico mutagenesis of RNA splicing in HIV-1.
pubmed:affiliation
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 3633 Engineering Hall, 1415 Engineering Drive, Madison, Wisconsin 53706-1607, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.