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Related Concept Videos

MicroRNAs01:22

MicroRNAs

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 ends...

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mirTarRnaSeq: An R/Bioconductor Statistical Package for miRNA-mRNA Target Identification and Interaction Analysis.

Mercedeh Movassagh1, Sarah U Morton2, Christine Hehnly3

  • 1Dana Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, United States.

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Summary

We developed mirTarRnaSeq, a new R package to analyze microRNA-messenger RNA interactions. This tool helps identify key gene regulatory networks in diseases like stomach adenocarcinoma and COVID-19.

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • MicroRNA (miRNA) and messenger RNA (mRNA) interactions play crucial roles in gene regulation.
  • Accurate quantitative assessment of these relationships within sample cohorts is essential for understanding biological processes and disease mechanisms.
  • Existing tools may lack the statistical rigor or specific functionalities needed for comprehensive miRNA-mRNA interaction analysis.

Purpose of the Study:

  • To introduce mirTarRnaSeq, an R/Bioconductor package designed for the quantitative assessment of miRNA-mRNA relationships.
  • To provide a statistical framework for exploring predicted or pre-hypothesized miRNA-mRNA interactions.
  • To demonstrate the utility of mirTarRnaSeq through two distinct biological use cases.

Main Methods:

  • Development of the mirTarRnaSeq package in R/Bioconductor.
  • Application 1: Analysis of Epstein-Barr virus (EBV) miRNAs and their interactions with human and viral transcriptomes in stomach adenocarcinoma.
  • Application 2: Investigation of miRNA-mRNA dynamics in SARS-CoV-2 (COVID-19) infected lung epithelial cells using paired miRNA and RNA sequencing data across multiple time points (4, 12, and 24 hours post-infection).

Main Results:

  • In stomach adenocarcinoma, mirTarRnaSeq identified enrichment of mRNA targets highly expressed in specific immune and endothelial cell populations.
  • In COVID-19 infection, mirTarRnaSeq revealed evidence of human miRNAs targeting cytokine signaling and neutrophil regulation pathways.
  • Three predicted immune-specific mRNA-miRNA relationships from the COVID-19 lung epithelial cell model were found to be differentially expressed in patient blood samples, confirming clinical relevance.

Conclusions:

  • mirTarRnaSeq is a robust statistical tool for the quantitative assessment of miRNA-mRNA interactions in various biological contexts.
  • The package facilitates the identification of biologically relevant miRNA-mRNA relationships, aiding in target prediction and hypothesis generation.
  • mirTarRnaSeq can address a wide range of biological questions, improving the prediction and understanding of miRNA-mRNA interactions in health and disease.