A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing
A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing
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DOI：
10.1261/rna.2442211
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发表时间：
2011-08-01
期刊：
影响因子：
4.5
通讯作者：
Blelloch, Robert
中科院分区：
文献类型：
--
作者：
Babiarz, Joshua E.;Hsu, Ruby;Blelloch, Robert
非典型微小RNA（miRNAs）和内源性小干扰RNA（endo-siRNAs）是小RNA的不同亚类，它们绕过DGCR 8/DROSHA微处理器，但仍然需要DICER 1进行生物合成。它们在哺乳动物中的作用（如果有的话）仍然未知。为了确定这些亚类的潜在功能特性，我们比较了有丝分裂后神经元中Dgcr 8与Dicer 1的条件性缺失所导致的表型。Dicer 1的丢失导致较早的致死性，更严重的结构异常，并增加相对于Dgcr 8损失的细胞凋亡。对来自条件性敲除和对照同窝仔的海马和皮质的小RNA进行深度测序，鉴定了多种非典型microRNA，其在脑中相对于其他组织以高水平表达，包括mirtron和H/ACA snoRNA衍生的小RNA。相比之下，我们在大脑中没有发现endo-siRNAs的证据。总之，我们的研究结果提供了证据表明，一个不同的人口高度表达的非典型的miRNA，一起可能发挥重要的功能作用，在有丝分裂后的神经元。
Noncanonical microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs) are distinct subclasses of small RNAs that bypass the DGCR8/DROSHA Microprocessor but still require DICER1 for their biogenesis. What role, if any, they have in mammals remains unknown. To identify potential functional properties for these subclasses, we compared the phenotypes resulting from conditional deletion of Dgcr8 versus Dicer1 in post-mitotic neurons. The loss of Dicer1 resulted in an earlier lethality, more severe structural abnormalities, and increased apoptosis relative to that from Dgcr8 loss. Deep sequencing of small RNAs from the hippocampus and cortex of the conditional knockouts and control littermates identified multiple noncanonical microRNAs that were expressed at high levels in the brain relative to other tissues, including mirtrons and H/ACA snoRNA-derived small RNAs. In contrast, we found no evidence for endo-siRNAs in the brain. Taken together, our findings provide evidence for a diverse population of highly expressed noncanonical miRNAs that together are likely to play important functional roles in post-mitotic neurons.