Branched kissing loops for the construction of diverse RNA homooligomeric nanostructures

Branched kissing loops for the construction of diverse RNA homooligomeric nanostructures
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DOI:
10.1038/s41557-019-0406-7
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发表时间:
2020-01-20
期刊:
影响因子:
21.8
通讯作者:
Weizmann, Yossi
Weizmann, Yossi
中科院分区:
化学1区
文献类型:
--
作者:
Liu, Di;Geary, Cody W.;Weizmann, Yossi

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在生物系统中,大而复杂的结构通常由多个简单的相同亚基组装而成。这种策略-同源寡聚化-允许结构的有效遗传编码,并且避免了控制多个不同单元的化学计量的需要。当设计人工核酸结构时,它还允许最小数量的不同亚基。在这里,我们提出了一个强大的自组装系统,其中homooligomerizable瓷砖形成分子内折叠的RNA单链。瓦片通过人工设计的分支的吻环基序连接,涉及膨胀螺旋和发夹环的单链区域之间的沃森-克里克碱基配对。通过调整瓷砖的几何形状,以获得控制的曲率,扭转和螺旋的数量,我们已经构建了16个不同的线性和圆形结构,包括一个有限大小的三维笼。我们进一步证明了基于分支接吻环的瓷砖的共转录自组装,并表明插入到转移RNA支架中的瓷砖可以在细菌cells.Homooligomerization系统中过表达,可用于构建纳米结构并帮助理解天然类似物。但是,要形成这种结构多样性和复杂性与生物系统相当的人工系统是一项挑战。现在,已经设计了一种人工分支的接吻环基序,它连接从单链RNA折叠的瓦片,以产生不同的同源寡聚纳米结构。
In biological systems, large and complex structures are often assembled from multiple simpler identical subunits. This strategy-homooligomerization-allows efficient genetic encoding of structures and avoids the need to control the stoichiometry of multiple distinct units. It also allows the minimal number of distinct subunits when designing artificial nucleic acid structures. Here, we present a robust self-assembly system in which homooligomerizable tiles are formed from intramolecularly folded RNA single strands. Tiles are linked through an artificially designed branched kissing-loop motif, involving Watson-Crick base pairing between the single-stranded regions of a bulged helix and a hairpin loop. By adjusting the tile geometry to gain control over the curvature, torsion and the number of helices, we have constructed 16 different linear and circular structures, including a finite-sized three-dimensional cage. We further demonstrate cotranscriptional self-assembly of tiles based on branched kissing loops, and show that tiles inserted into a transfer RNA scaffold can be overexpressed in bacterial cells.Homooligomerization systems can be used to construct nanoarchitectures and to aid understanding of natural analogues. But the formation of such artificial systems with structural diversity and complexity comparable to that of biological systems is challenging. Now, an artificial branched kissing-loop motif has been designed, which links tiles folded from a single strand of RNA to give diverse homooligomeric nanostructures.