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Evolutionary Divergence of Brain-specific Precursor Mirnas Drives Efficient Processing and Production of Mature Mirnas in Human

Neuroscience(2018)SCI 3区

Univ Dhaka

Cited 4|Views12
Abstract
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 Intriguingly, in human brain, expression levels of these miRNAs superseded the levels of the ubiquitously expressed "Common-miRNAs".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.
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miRNA,secondary structure,evolution,human-brain,gene-expression,gene-regulatory network
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要点】:研究揭示了人脑特异性的前体micro-RNAs在进化过程中的显著差异,这些差异促进了成熟micro-RNAs的高效处理和产生,对人类大脑发育至关重要。

方法】:通过分类miRNAs为脑特异性、非脑特异性及常见类型,比较不同物种间这些miRNAs前体结构区域的序列差异,并分析其在不同组织中的表达水平。

实验】:研究使用了人类、非人类灵长类和啮齿动物的序列数据,通过跨组织表达分析及基因调控网络的重建,发现人脑特异性miRNAs的高表达及其在miRNA处理中的高效性。