SV40 T-antigen-binding sites within the 5'-flanking regions of human U1 and U2 genes.
SV40 T-antigen-binding sites within the 5'-flanking regions of human U1 and U2 genes.
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人类 U1 和 U2 基因 5 侧翼区域内的 SV40 T 抗原结合位点。
DOI：
10.1016/0378-1119(91)90612-f
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发表时间：
1991
期刊：
影响因子：
3.5
通讯作者：
Prives,C
中科院分区：
文献类型：
--
作者：
Han,YM;Dahlberg,J;Lund,E;Manley,JL;Prives,C
编码人类 U1 和 U2 小核 RNA (snRNA) 的基因 (U1 和 U2) 的 5' 侧翼区域各自包含与猿病毒 (SV40) 大肿瘤抗原 (T·Ag) 特异性结合的序列。用缺乏 T·Ag 结合位点的序列替换这些位点并不能阻止 U1 或 U2 snRNA 在多种细胞类型中的积累，但删除这些区域会导致表达完全丧失。因此，这些序列可能仅起到间隔功能，并且T·Ag结合位点似乎对于表达不是必需的。然而，T·Ag 的共表达显着降低了含有高亲和力 T·Ag 结合位点（来自 SV40 基因组）代替 U1T·Ag 结合位点的 U1 基因的表达。相反，T·Ag 的共表达增强了 U2 的合成，但不增强 U1、snRNA 的合成，与 T·Ag 结合位点的存在无关。因此，虽然 U1 和 U2 启动子区域内共有的 T·Ag 结合位点似乎不影响表达，但 SV40 T·Ag 与高亲和力位点的结合可导致强 snRNA 启动子的显着抑制，并且在缺乏已知结合位点的情况下，T·Ag 可以增强另一个启动子的表达。
The 5′ flanking regions of the genes (U1andU2) encoding the human U1 and U2 small nuclear RNAs (snRNAs) each contain sequences that bind specifically to the simian virus (SV40) large tumor antigen (T·Ag). Substitution of these sites with sequences that lack T·Ag-binding sites did not block accumulation of U1 or U2 snRNA in a variety of cell types, but deletion of these regions resulted in the total loss of expression. Thus, these sequences may serve only a spacing function, and the T·Ag-binding sites appear not to be necessary for expression. However, coexpression of T·Ag markedly reduced expression of aU1gene containing a high-affinity T·Ag-binding site (from the SV40 genome) in place of theU1T·Ag-binding site. In contrast, coexpression of T·Ag enhanced synthesis of U2, but not U1, snRNA, independent of the presence of the T·Ag-binding sites. Thus, while the consensus T·Ag-binding sites within theU1andU2promoter regions do not appear to influence expression, the binding of SV40 T·Ag to a high-affinity site can lead to significant repression of a strong snRNA promoter, and T·Ag can enhance expression of another in the absence of a known binding site.