tailieunhanh - Báo cáo y học: " A suboptimal 5' splice site downstream of HIV-1 splice site A1 is required for unspliced viral mRNA accumulation and efficient virus replication"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: A suboptimal 5' splice site downstream of HIV-1 splice site A1 is required for unspliced viral mRNA accumulation and efficient virus replication | Retrovirology BioMed Central Research Open Access A suboptimal 5 splice site downstream of HIV-I splice site A1 is required for unspliced viral mRNA accumulation and efficient virus replication Joshua M Madsen1 and C Martin Stoltzfus 1 2 Address 1Interdisciplinary Program in Molecular Biology University of Iowa Iowa City IA 52242 USA and 2Department of Microbiology University of Iowa Iowa City IA 52242 USA Email Joshua M Madsen - joshua-madsen@ C Martin Stoltzfus - marty-stoltzfus@ Corresponding author Published 03 February 2006 Received 13 December 2005 Retrovirology 2006 3 10 doi 1742-4690-3-10 Accepted 03 February 2006 This article is available from http content 3 1 10 2006 Madsen and Stoltzfus licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background Inefficient alternative splicing of the human immunodeficiency virus type 1 HIV-1 primary RNA transcript results in greater than half of all viral mRNA remaining unspliced. Regulation of HIV-1 alternative splicing occurs through the presence of suboptimal viral 5 and 3 splice sites 5 and 3 ss which are positively regulated by exonic splicing enhancers ESE and negatively regulated by exonic splicing silencers ESS and intronic splicing silencers ISS . We previously showed that splicing at HIV-1 3 ss A2 is repressed by ESSV and enhanced by the downstream 5 ss D3 signal. Disruption of ESSV results in increased vpr mRNA accumulation and exon 3 inclusion decreased accumulation of unspliced viral mRNA and decreased virus production. Results Here we show that optimization of the 5 ss D2 signal results in increased splicing at the upstream 3 ss A1 increased inclusion of exon 2 into viral mRNA decreased accumulation of .