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 Intriguingly, in human brain, expression levels of these miRNAs superseded the levels of the ubiquitously expressed "Common-miRNAs".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.

Original languageEnglish
Pages (from-to)141-159
Number of pages19
JournalNeuroscience
Volume392
DOIs
Publication statusPublished - 10 Nov 2018

ID: 44061804