The hammerhead self-cleaving motif as a precursor to complex endonucleolytic ribozymes.
The hammerhead self-cleaving motif as a precursor to complex endonucleolytic ribozymes.
复制标题
锤头自切割基序作为复杂核酸内切核酶的前体。
DOI：
10.1261/rna.078813.121
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Piccirilli JA
中科院分区：
文献类型：
--
作者：
DasGupta S;Nykiel K;Piccirilli JA
通过保留催化功能的突变网络（中性网络），不同催化 RNA 基序之间的联系可能是生物催化进化的核心。尽管有人认为功能性 RNA 共同形成一个相互连接的中性网络网络，但几乎没有证据表明天然存在的 RNA 中存在这种交叉网络。在这里，我们展示了两种天然存在的、看似无关的核酸内切核酶——锤头（HH）和发夹（HP）——的中性网络相交。这些网络交叉处的序列通过潜在地填充两个催化折叠而表现出与两种核酶相对应的催化功能，并实现两者之间的平滑交叉。像HH核酶这样的小而结构简单的核酸内切基序可以通过沿着中性网络的突变行走，遇到新的催化表型，并且这些网络交叉点上结构灵活的双功能序列可以充当RNA世界中进化多样化的节点。考虑到 HH 核酶的简单性和小尺寸，我们认为这种自切割基序可能是其他更复杂的核酸内切核酶的前体。更一般地说，我们的结果表明，具有不同序列、结构和催化功能的 RNA 可能通过序列空间中的突变连接来共享进化历史。
Connections between distinct catalytic RNA motifs through networks of mutations that retain catalytic function (neutral networks) were likely central to the evolution of biocatalysis. Despite suggestions that functional RNAs collectively form an interconnected web of neutral networks, little evidence has emerged to demonstrate the existence of such intersecting networks in naturally occurring RNAs. Here we show that neutral networks of two naturally occurring, seemingly unrelated endonucleolytic ribozymes, the hammerhead (HH) and hairpin (HP), intersect. Sequences at the intersection of these networks exhibit catalytic functions corresponding to both ribozymes by potentially populating both catalytic folds and enable a smooth crossover between the two. Small and structurally simple endonucleolytic motifs like the HH ribozyme could, through mutational walks along their neutral networks, encounter novel catalytic phenotypes, and structurally flexible, bifunctional sequences at the intersection of these networks could have acted as nodes for evolutionary diversification in an RNA world. Considering the simplicity and small size of the HH ribozyme, we propose that this self-cleaving motif could have been a precursor to other more complex endonucleolytic ribozymes. More generally, our results suggest that RNAs that possess distinct sequences, structures, and catalytic functions, can potentially share evolutionary history through mutational connections in sequence space.
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影响因子：
4.5
作者：
Huang, Z;Szostak, JW
通讯作者：
Szostak, JW
DOI：
10.3390/molecules22010078
发表时间：
2017-01-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
de la Peña M;García-Robles I;Cervera A
通讯作者：
Cervera A
DOI：
10.1073/pnas.86.18.7054
发表时间：
1989-09-01
影响因子：
11.1
作者：
BENNER, SA;ELLINGTON, AD;TAUER, A
通讯作者：
TAUER, A
DOI：
10.3390/molecules21111570
发表时间：
2016-11-18
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Lau MW;Ferré-D'Amaré AR
通讯作者：
Ferré-D'Amaré AR
影响因子：
9.8
作者：
Bendixsen, Devin P.;Collet, James;Hayden, Eric J.
通讯作者：
Hayden, Eric J.