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 journalArticlepeer-review

Abstract

Micro(mi)RNAs are short double stranded noncoding RNAs (19-23nts) 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 6 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’s 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.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Nov 12 2019
Externally publishedYes

Keywords

  • cell death
  • DISE
  • RNAi
  • survival genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of '6mer seed toxicity in viral microRNAs'. Together they form a unique fingerprint.

Cite this