How is polyadenylation restricted to 3'-untranslated regions?
How is polyadenylation restricted to 3'-untranslated regions?
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聚腺苷酸化如何限制在 3-非翻译区域？
DOI：
10.1002/yea.3915
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Struhl,Kevin
中科院分区：
文献类型：
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作者：
Struhl,Kevin
聚腺苷酸化发生在3′‐非翻译区（3′‐utr）的许多位点，但很少发生在编码区。Pol II如何穿过长编码区而不产生聚(A)位点，然而一旦到达3 '‐UTR就允许混杂聚腺苷化？切割/聚腺苷酸化（CpA）机制优先与3 ' - utr相关，但在Pol II延伸期间，其招募如何仅限于3 ' - utr尚不清楚。与编码区不同，3′‐utr具有很长的富含AT的DNA片段，这对于限制3′‐utr的聚腺苷化可能很重要。3′‐UTR的识别可以发生在DNA （at‐富）、RNA （AU‐富）或RNA:DNA杂交（rU:dA‐和/或rA:dT‐富）水平。基于对3′‐UTR识别至关重要的核酸，对于CpA机制如何选择性地招募到3′‐UTR，从而限制聚腺苷化发生的位置，有三种不相互排斥的模型：(1)基于RNA的模型表明，CpA复合体直接（或间接通过一个或多个中间蛋白）结合在Pol II通过这些区域后暴露的富含AU的长片段。(2)基于DNA的模型表明，富含AT的序列影响核小体耗竭或延长Pol II机制，导致一些延长因子的解离和随后的CpA机制的募集。(3) RNA:DNA杂交模型表明，连接核苷酸加成位点和RNA退出位点的rU:dA -和/或rA:dT -富双链上Pol II延伸复合物的优先失稳，允许CpA机制与3 ' - utr优先结合。建议进行实验，为其中一个或多个模型提供证据。
Polyadenylation occurs at numerous sites within 3′‐untranslated regions (3′‐UTRs) but rarely within coding regions. How does Pol II travel through long coding regions without generating poly(A) sites, yet then permits promiscuous polyadenylation once it reaches the 3′‐UTR? The cleavage/polyadenylation (CpA) machinery preferentially associates with 3′‐UTRs, but it is unknown how its recruitment is restricted to 3′‐UTRs during Pol II elongation. Unlike coding regions, 3′‐UTRs have long AT‐rich stretches of DNA that may be important for restricting polyadenylation to 3′‐UTRs. Recognition of the 3′‐UTR could occur at the DNA (AT‐rich), RNA (AU‐rich), or RNA:DNA hybrid (rU:dA‐ and/or rA:dT‐rich) level. Based on the nucleic acid critical for 3′‐UTR recognition, there are three classes of models, not mutually exclusive, for how the CpA machinery is selectively recruited to 3′‐UTRs, thereby restricting where polyadenylation occurs: (1) RNA‐based models suggest that the CpA complex directly (or indirectly through one or more intermediary proteins) binds long AU‐rich stretches that are exposed after Pol II passes through these regions. (2) DNA‐based models suggest that the AT‐rich sequence affects nucleosome depletion or the elongating Pol II machinery, resulting in dissociation of some elongation factors and subsequent recruitment of the CpA machinery. (3) RNA:DNA hybrid models suggest that preferential destabilization of the Pol II elongation complex at rU:dA‐ and/or rA:dT‐rich duplexes bridging the nucleotide addition and RNA exit sites permits preferential association of the CpA machinery with 3′‐UTRs. Experiments to provide evidence for one or more of these models are suggested.