6mer seed toxicity in viral microRNAs

Murmann, A. E.; Bartom, E. T.; Schipma, M. J.; Vilker, J.; Chen, S.; Peter, M. E.

doi:10.1101/838979

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bioRxiv · 10.1101/838979

6mer seed toxicity in viral microRNAs

Murmann, A. E.·Bartom, E. T.·Schipma, M. J.·Vilker, J.·Chen, S.·Peter, M. E.

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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 Kaposis 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.

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Murmann, A. E., Bartom, E. T., Schipma, M. J., Vilker, J., Chen, S., Peter, M. E.. 2019-11-12. 6mer seed toxicity in viral microRNAs. https://doi.org/10.1101/838979

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