6mer Seed Toxicity in Viral microRNAs

Andrea E. Murmann, Elizabeth T. Bartom, Matthew J. Schipma, Jacob Vilker, Siquan Chen, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

MicroRNAs (miRNAs) are short double-stranded noncoding RNAs (19-23 nucleotides) that regulate gene expression by suppressing mRNAs through RNA interference. Targeting is determined by the seed sequence (position 2-7/8) of the mature miRNA. A minimal G-rich seed of just six nucleotides is highly toxic to cells by targeting genes essential for cell survival. A screen of 215 miRNAs encoded by 17 human pathogenic viruses (v-miRNAs) now suggests that a number of v-miRNAs can kill cells through a G-rich 6mer sequence embedded in their seed. Specifically, we demonstrate that miR-K12-6-5p, an oncoviral mimic of the tumor suppressive miR-15/16 family encoded by human Kaposi sarcoma-associated herpes virus, harbors a noncanonical toxic 6mer seed (position 3-8) and that v-miRNAs are more likely than cellular miRNAs to utilize a noncanonical 6mer seed. Our data suggest that during evolution viruses evolved to use 6mer seed toxicity to kill cells. Molecular Genetics; Virology; Bioinformatics

Original languageEnglish (US)
Article number100737
JournaliScience
Volume23
Issue number2
DOIs
StatePublished - Feb 21 2020

Keywords

  • Bioinformatics
  • Molecular Genetics
  • Virology

ASJC Scopus subject areas

  • General

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