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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Evolution of microRNA in primates.

Jey C McCreight1, Sean E Schneider1,2, Damien B Wilburn1

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We experimentally validated hundreds of microRNAs (miRNAs) across thirteen primate species, revealing conserved and novel miRNA evolution. This research sheds light on miRNA roles in primate evolution, particularly in neuronal processes.

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Molecular biology

Background:

  • MicroRNAs (miRNAs) are crucial for post-transcriptional gene regulation, impacting thousands of messenger RNA targets.
  • Primate miRNA evolution is understudied, with most non-human primate miRNAs predicted computationally without experimental validation.
  • Understanding miRNA evolution is key to comprehending phenotypic changes and human evolutionary history.

Purpose of the Study:

  • To experimentally validate and characterize microRNA evolution across a wide range of primate species.
  • To identify conserved and divergent miRNA sequences and structures throughout primate phylogeny.
  • To investigate the role of novel or altered miRNAs in primate evolutionary adaptations, especially in neuronal processes.

Main Methods:

  • Sequencing of thirteen diverse primate species representing various phylogenetic positions.
  • Experimental validation of hundreds of microRNAs (miRNAs).
  • Comparative genomic analysis of miRNA sequences and pre-miRNA hairpin structures.

Main Results:

  • Hundreds of microRNAs (miRNAs) were experimentally validated, tripling the number of species with validated miRNAs.
  • High conservation of miRNA seed regions and mature sequences was observed across primates, alongside conserved pre-miRNA hairpin structures.
  • Notable exceptions included structural changes in miR-501 leading to seed shifts and an expansion of miR-320 paralogs, with many non-conserved miRNAs potentially regulating neuronal processes.

Conclusions:

  • MicroRNA evolution in primates shows both high conservation and significant divergence, offering insights into regulatory plasticity.
  • The identification of novel and altered miRNAs, particularly those affecting neuronal pathways, highlights their importance in primate evolution.
  • This study significantly expands the experimentally validated repertoire of primate miRNAs and provides a foundation for future research into miRNA function and evolution.