Challenges of ligand identification for the second wave of orphan riboswitch candidates
Challenges of ligand identification for the second wave of orphan riboswitch candidates
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DOI：
10.1080/15476286.2017.1403002
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发表时间：
2018-01-01
期刊：
影响因子：
4.1
通讯作者：
Breaker, Ronald R.
中科院分区：
文献类型：
--
作者：
Greenlee, Etienne B.;Stav, Shira;Breaker, Ronald R.
孤儿核糖开关候选者是非编码RNA基序，其代表被认为具有遗传调控元件的功能，但其靶配体尚未确定。对某些孤儿的研究，特别是多年来一直抵制实验验证的类别，一旦确定了其配体，就发现了重要的生物学途径和过程。之前，我们重点介绍了四种最常见和最有趣的孤儿核糖开关候选者的详细信息。这有助于验证信号分子 c-di-AMP、ZTP 和 ppGpp、金属离子 Mn2+ 以及代谢物胍和 PRPP 的核糖开关。此类研究还产生了核糖开关感知的配体与许多生化途径之间的有用联系。在本报告中，我们描述了 30 种不同类别的孤儿核糖开关候选物的已知特征，其中一些特征十多年来仍未得到解决。我们还讨论了通过对这些 RNA 进行重点研究来发现新的生物学见解的前景。最后，我们为寻找这些神秘 RNA 配体的实验目标提出建议。
Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn2+, and the metabolites guanidine and PRPP. Such studies also yield useful linkages between the ligands sensed by the riboswitches and numerous biochemical pathways. In the current report, we describe the known characteristics of 30 distinct classes of orphan riboswitch candidates - some of which have remained unsolved for over a decade. We also discuss the prospects for uncovering novel biological insights via focused studies on these RNAs. Lastly, we make recommendations for experimental objectives along the path to finding ligands for these mysterious RNAs.