Expanding the microRNA targeting code: functional sites with centered pairing.
Expanding the microRNA targeting code: functional sites with centered pairing.
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DOI：
10.1016/j.molcel.2010.06.005
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发表时间：
2010-06-25
期刊：
影响因子：
16
通讯作者：
Bartel DP
中科院分区：
文献类型：
--
作者：
Shin C;Nam JW;Farh KK;Chiang HR;Shkumatava A;Bartel DP
大多数后生动物microRNA靶点与种子区有完美的配对，位于miRNA 5 '端附近。虽然配对到3 '区有时补充种子匹配或补偿错配，配对到中心区域已经知道只在传递agronaute催化的mRNA切割的罕见位点起作用。在这里，我们提出了“中心位点”，一类microRNA靶位点缺乏完美的种子配对和3 '补偿配对，而是有11-12个连续的沃森-克里克对到microRNA的中心。虽然中心位点在体外（在Mg2+升高的情况下）可以促进mRNA的切割，但在细胞中，它们抑制蛋白质输出，而没有相应的agronaute催化的切割。我们的研究还发现了在培养细胞和人脑中广泛配对的裂解底物位点。这种扩展的切割靶点和中心位点类型的鉴定有助于解释为什么许多microrna的中心区域在进化上是保守的。
Most metazoan microRNA target sites have perfect pairing to the seed region, located near the miRNA 5’ end. Although pairing to the 3’ region sometimes supplements seed matches or compensates for mismatches, pairing to the central region has been known to function only at rare sites that impart Agronaute-catalyzed mRNA cleavage. Here we present “centered sites,” a class of microRNA target sites that lacks both perfect seed pairing and 3’-compensatory pairing and instead has 11–12 contiguous Watson–Crick pairs to the center of the microRNA. Although centered sites can impart mRNA cleavage in vitro (in elevated Mg2+), in cells they repress protein output without consequential Agronaute-catalyzed cleavage. Our study also identified extensively paired sites that are cleavage substrates in cultured cells and human brain. This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many microRNAs are evolutionarily conserved.
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