THE ROLE OF ADARS-INTERACTING RNA HELICASES IN SHAPING THE RNA EDITOME IN CANCER

Adenosine-to-inosine (A-to-I) RNA editing, primarily catalysed by the ADAR family of proteins, is oftentimes dysregulated in cancers. However, the regulatory mechanisms controlling editing frequency in cancer cells remain largely elusive. Besides factors affecting the expression and activity of ADAR proteins, ADARs-interacting proteins are known to orchestrate editing regulation. From our co-immunoprecipitation coupled with mass spectrometry analysis, we identified 23 RNA helicases as ADARs interactors, most having an unknown role in A-to-I editing. Employing an unbiased transcriptome-wide A-to-I editing analysis, I unravelled that 6 of these ADARs-interacting RNA helicases could reshape the A-to-I editome in a bidirectional, enhancive, or repressive fashion in cancer cells. I further investigated two bidirectional regulators DHX9 and DDX21, with oncogenic functions, that regulate distinct subsets of editing sites plausibly via RNA-binding dependent and independent mechanisms respectively. My findings illustrate crucial insights about the mechanistic underpinnings of A-to-I editing regulation mediated by ADARs-interacting RNA helicases.

Author dc:creator

• PRIYANKAA PITCHESHWAR

• A-to-I RNA editing, bidirectional regulators, cancer