Identification of positive and negative splicing regulatory elements within the terminal tat-rev exon of human immunodeficiency virus type 1

Identification of positive and negative splicing regulatory elements within the terminal tat-rev exon of human immunodeficiency virus type 1
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1 型人类免疫缺陷病毒末端 tat-rev 外显子内正剪接和负剪接调控元件的鉴定

DOI:
10.1128/mcb.15.8.4597
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发表时间:
1995
影响因子:
5.3
通讯作者:
Andalan Cochrane
Andalan Cochrane
中科院分区:
生物学2区
文献类型:
--
作者:
Alfredo Staffa;Andalan Cochrane

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The requirement of human immunodeficiency virus type 1 to generate numerous proteins from a single primary transcript is met largely by the use of suboptimal splicing to generate over 30 mRNAs. To ensure that appropriate quantities of each protein are produced, there must be a signal(s) that controls the efficiency with which any particular splice site in the RNA is used. To identify this control element(s) and to understand how it operates to generate the splicing pattern observed, we have initially focused on the control of splicing of the tat-rev intron, which spans the majority of the env open reading frame. Previous analysis indicated that a suboptimal branchpoint and polypyridimine tract in this intron contribute to its suboptimal splicing (A. Staffa and A. Cochrane, J. Virol. 68:3071-3079, 1994). In this report, we identify two additional elements within the 3'-terminal exon, an exon-splicing enhancer (ESE) and an exon splicing silencer (ESS), that modulate the overall efficiency with which the 3' tat-rev splice site is utilized. Both elements are capable of functioning independently of one another. Furthermore, while both the ESE and ESS can function in a heterologous context, the function of the ESS is extremely sensitive to the sequence context into which it is placed. In conclusion, it would appear that the presence of a suboptimal branchpoint and a polypyrimidine tract as well as the ESE and ESS operate together to yield the balanced splicing of the tat-rev intron observed in vivo.
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