Targeted inhibition of WRN helicase by external guide sequence and RNase P RNA

Anna Hitrik, Ghada Abboud-Jarrous, Natalie Orlovetskie, Raphael Serruya, Nayef Jarrous*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Human WRN, a RecQ helicase encoded by the Werner syndrome gene, is implicated in genome maintenance, including replication, recombination, excision repair and DNA damage response. These genetic processes and expression of WRN are concomitantly upregulated in many types of cancers. Therefore, targeted destruction of this helicase could be useful for elimination of cancer cells. Here, we provide a proof of concept for applying the external guide sequence (EGS) approach in directing an RNase P RNA to efficiently cleave the WRN mRNA in cultured human cell lines, thus abolishing translation and activity of this distinctive 3'-5' DNA helicase-nuclease. Remarkably, EGS-directed knockdown of WRN leads to severe inhibition of cell viability. Hence, further assessment of this targeting system could be beneficial for selective cancer therapies, particularly in the light of the recent improvements introduced into EGSs.

Original languageAmerican English
Pages (from-to)572-580
Number of pages9
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1859
Issue number4
DOIs
StatePublished - 1 Apr 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier B.V.

Keywords

  • External guide sequence
  • RNase P RNA
  • WRN helicase, selective cancer therapy
  • Werner syndrome

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