RNA catalyses nuclear pre-mRNA splicing.
RNA catalyses nuclear pre-mRNA splicing.
复制标题
RNA催化核前MRNA剪接。
DOI：
10.1038/nature12734
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发表时间：
2013-11-14
期刊：
影响因子：
64.8
通讯作者：
Piccirilli JA
中科院分区：
文献类型：
--
作者：
Fica SM;Tuttle N;Novak T;Li NS;Lu J;Koodathingal P;Dai Q;Staley JP;Piccirilli JA
在核前信使RNA剪接中，内含子被剪接体切除，剪接体是由蛋白质和小核RNA（snRNA）组成的多兆道尔顿机器。三十多年前，随着自我剪接II组内含子RNA的发现，snRNA被假设为催化剪接。然而，迄今为止，还没有确切的证据表明RNA或蛋白质在剪接体催化中的作用。通过使用金属救援策略，在这里，我们表明，U6 snRNA催化两个剪接反应，通过定位二价金属，稳定在每个反应的离去基团。引人注目的是，我们鉴定的所有U6催化金属配体对应于观察到的在II组内含子RNA的晶体结构中定位催化二价金属的配体。这些发现表明，第二组内含子和剪接体共享共同的催化机制，并可能共同的进化起源。我们的研究结果表明，RNA介导的剪接体内的催化。
In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a multi-megadalton machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, following the discovery of self-splicing group II intron RNAs, the snRNAs were hypothesized to catalyze splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported to date. By using metal rescue strategies, here we show that the U6 snRNA catalyzes both splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Strikingly, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms, and likely common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.