Mutagen-specific mutation signature determines global microRNA binding

Eyal Greenberg, Gideon Rechavi, Ninette Amariglio, Oz Solomon, Jacob Schachter, Gal Markel, Eran Eyal

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3′UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3′UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3′UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation.

Original languageEnglish
Article numbere27400
JournalPLoS ONE
Volume6
Issue number11
DOIs
StatePublished - 9 Nov 2011
Externally publishedYes

Fingerprint

Dive into the research topics of 'Mutagen-specific mutation signature determines global microRNA binding'. Together they form a unique fingerprint.

Cite this