Splicing regulatory elements within tat exon 2 of human immunodeficiency virus type 1 (HIV-1) are characteristic of group M but not group OHIV-1 strains
Splicing regulatory elements within tat exon 2 of human immunodeficiency virus type 1 (HIV-1) are characteristic of group M but not group OHIV-1 strains
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DOI：
10.1128/jvi.73.12.9764-9772.1999
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发表时间：
1999-12-01
影响因子：
5.4
通讯作者：
Stoltzfus, CM
中科院分区：
文献类型：
--
作者：
Bilodeau, PS;Domsic, JK;Stoltzfus, CM
在人类免疫缺陷病毒1型（HIV-1）的NL 4 -3株中，负责达特、rev和env/nef 3'剪接位点处选择性剪接的相对效率的调节元件（A3至A5）包含在达特外显子2及其侧翼序列的区域内。影响达特、rev和env/nef mRNA剪接的两个元件已定位于该区域，首先，位于用于产生脂肪mRNA的3 ′剪接位点下游约70个核苷酸处的NL 4 -3中的外显子剪接沉默子（ESS 2）特异性地抑制该剪接位点处的剪接。第二，Mb 3'剪接位点是三个rev 3'剪接位点中最下游的，也作为抑制env/nef 3'剪接位点A5处剪接的元件。这些元素是保守的，在一些但不是所有的HIV-1株，这些序列的变化对剪接的影响已经在细胞转染和体外剪接试验中进行了研究。SF 2是另一个进化枝B病毒，也是主要（M组）病毒的成员，在ESS 2内有几个序列变化，并使用不同的rev 3'剪接位点。然而，与NL 4 -3类似，剪接被两个元件抑制。与NL 4 -3菌株一样，SF 2 Mb AG二核苷酸与A5分支点重叠，因此抑制作用可能是由两种不同剪接因子的相同位点竞争引起的。ANT 70 C是高度分化的离群（O组）病毒的成员，其序列变化更广泛，脂肪外显子2中不存在ESS 2活性。O组病毒也缺少在所有M组病毒中保守的rev 3'剪接位点Mb，ANT 70 C最下游的rev 3'剪接位点的突变不增加A5处的剪接，并且所有分支点都在两个rev 3'剪接位点的上游，因此，达特外显子2中的剪接调节元件是大多数M组HIV-1毒株的特征，但在O组HIV-1毒株中不存在。
In the NL4-3 strain of human immunodeficiency virus type 1 (HIV-1), regulatory elements responsible for the relative efficiencies of alternative splicing at the tat, rev, and the env/nef 3' splice sites (A3 through A5) are contained within the region of tat exon 2 and its flanking sequences, Two elements affecting splicing of tat, rev, and env/nef mRNAs have been localized to this region, First, an exon splicing silencer (ESS2) in NL4-3, located approximately 70 nucleotides downstream from the 3' splice site used to generate fat mRNA, acts specifically to inhibit splicing at this splice site. Second, the Mb 3' splice site, which is the most downstream of the three rev 3' splice sites, also serves as an element inhibiting splicing at the env/nef 3' splice site A5. These elements are conserved in some but not all HIV-1 strains, and the effects of these sequence changes on splicing have been investigated in cell transfection and in vitro splicing assays. SF2, another clade B virus and member of the major (group M) viruses, has several sequence changes within ESS2 and uses a different rev 3' splice site. However, splicing is inhibited by the two elements similarly to NL4-3, As with the NL4-3 strain, the SF2 Mb AG dinucleotide overlaps an A5 branchpoint, and thus the inhibitory effect may result from competition of the same site for two different splicing factors. The sequence changes in ANT70C, a member of the highly divergent outlier (group O) viruses, are more extensive, and ESS2 activity in fat exon 2 is not present. Group O viruses also lack the rev 3' splice site Mb, which is conserved in all group M viruses, Mutagenesis of the most downstream rev 3' splice site of ANT70C does not increase splicing at A5, and all of the branchpoints are upstream of the two rev 3' splice sites, Thus, splicing regulatory elements in tat exon 2 which are characteristic of most group M HIV-1 strains are not present in group O HIV-1 strains.