Evolutionary Divergence of Brain-specific Precursor miRNAs Drives Efficient Processing and Production of Mature miRNAs in Human
Evolutionary Divergence of Brain-specific Precursor miRNAs Drives Efficient Processing and Production of Mature miRNAs in Human
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DOI：
10.1016/j.neuroscience.2018.09.010
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发表时间：
2018-11-10
期刊：
影响因子：
3.3
通讯作者：
Nabi, A. H. M. Nurun
中科院分区：
文献类型：
--
作者：
Chakraborty, Sajib;Islam, Md Rezaul;Nabi, A. H. M. Nurun
人类进化的标志包括大脑尺寸和复杂性的急剧增加。微小 RNA (miRNA) 及其靶基因错综复杂的相互作用对于大脑发育是不可或缺的。大脑特异性前体 miRNA (pre-miRNA) 不同结构区域的序列差异及其在人类相应成熟 miRNA 产生中的影响尚不清楚。为了解决这些问题，我们首先根据组织表达将miRNA分为三类：脑特异性（仅在大脑中表达）、非脑（在非脑组织中表达）和常见（在所有组织中表达），并比较了人类、非人灵长类动物和啮齿类动物不同结构区域（基底节、下茎和上茎、内部和末端环）的序列差异。我们的分析表明，与其他物种相比，人类大脑特异性 pre-miRNA 的不配对区域具有相对较高的进化分化率。跨组织表达分析揭示了与其他物种相比，人类脑特异性 miRNA 的表达更高。有趣的是，在人脑中，这些 miRNA 的表达水平取代了普遍表达的“Common-miRNA”的水平。进一步的分析表明，大脑特异性 pre-miRNA 中某些基序和核苷酸偏好的存在可能有利于 DROSHA 和 DICER 改善 miRNA 加工。人脑特异性 miRNA 的较高处理效率反映为人脑中相应成熟 miRNA 产量的增加。最后，基因调控网络的重建揭示了由大脑特异性 miRNA 驱动的不同途径，这些途径可能有助于人类大脑的发育。 (C) 2018 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
The hallmark of human evolution encompasses the dramatic increase in brain size and complexity. The intricate interplays of micro-RNAs (miRNAs) and their target genes are indispensable in brain development. Sequence divergence in distinct structural regions of Brain-specific precursor miRNAs (pre-miRNAs) and its consequence in the production of corresponding mature miRNAs in human are unknown. To address these questions, first we classified miRNAs into three categories based on tissue expression: Brain-specific (expressed exclusively in brain), Non-brain (expressed in Non-brain tissues) and Common (expressed in all tissues) and compared the sequence divergence of different structural regions (basal segment, lower and upper stem, internal and terminal loop) of categorized pre-miRNAs across human, non-human primates and rodents. Our analysis revealed that unpaired regions of Brain-specific pre-miRNAs in human bear traces of relatively high rate of evolutionary divergence compared to those in other species. Cross-tissue expression analysis unveiled the higher expression of the Brain-specific miRNAs in human compared to other species. Intriguingly, in human brain, expression levels of these miRNAs superseded the levels of the ubiquitously expressed "Common-miRNAs". Further analysis revealed that presence of certain motif and nucleotide preference in the Brain-specific pre-miRNAs may favor DROSHA and DICER to ameliorate miRNA processing. The higher processing efficiency of human Brain-specific miRNAs was reflected as an elevated production of corresponding mature miRNAs in the human brain. Finally, re-construction of gene-regulatory network uncovers different pathways driven by Brain-specific miRNAs that may contribute to the development of brain in human. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.