Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs
Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs
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DOI：
10.1093/nar/26.12.2891
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发表时间：
1998-06-15
影响因子：
14.9
通讯作者：
Wilusz, J
中科院分区：
文献类型：
--
作者：
Chen, F;Wilusz, J
我们先前已经将富含G的序列（GRS）确定为一个辅助下游元件（AUX DSE），它影响了SV40晚期聚腺苷酸化信号的加工效率。现在，我们已经确定核心U富元元素（URE）下游的序列形成了哺乳动物聚腺苷酸化信号的基本部分，这些新型的Aux DSE都通过稳定CSTF的组装在体外影响了3'-End处理的效率。核心下游URE，辅助DSE介导了在体外3'-End加工的三种可能机制。首先，AUX DSE可以通过在非结构化结构域中保持核心元素来促进加工效率核心下游URE，最后是GRS元素，而不是噬菌体R17涂层蛋白的结合位点可以代替对于腺病毒L3聚腺苷酸化信号的辅助下游区域。这表明AUX DSE结合蛋白可以通过稳定CSTF与RNA底物（Aux DSES）的结合来刺激3'末端加工中起积极作用可能是法规。
We have previously identified a G-rich sequence (GRS) as an auxiliary downstream element (AUX DSE) which influences the processing efficiency of the SV40 late polyadenylation signal. We have now determined that sequences downstream of the core U-rich element (URE) form a fundamental part of mammalian polyadenylation signals, These novel AUX DSEs all influenced the efficiency of 3'-end processing in vitro by stabilizing the assembly of CstF on the core downstream URE, Three possible mechanisms by which AUX DSEs mediate efficient in vitro 3'-end processing have been explored. First, AUX DSEs can promote processing efficiency by maintaining the core elements in an unstructured domain which allows the general polyadenylation factors to efficiently assemble on the RNA substrate, Second, AUX DSEs can enhance processing by forming a stable structure which helps focus binding of CstF to the core downstream URE, Finally, the GRS element, but not the binding site for the bacteriophage R17 coat protein, can substitute for the auxiliary downstream region of the adenovirus L3 polyadenylation signal. This suggests that AUX DSE binding proteins may play an active role in stimulating 3'-end processing by stabilizing the association of CstF with the RNA substrate, AUX DSEs, therefore, serve as a integral part of the polyadenylation signal and can affect signal strength and possibly regulation.