RT Journal Article
SR Electronic
T1 Principles governing A-to-I RNA editing in the breast cancer transcriptome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 012849
DO 10.1101/012849
A1 Debora Fumagalli
A1 David Gacquer
A1 Françoise Rothé
A1 Anne Lefort
A1 Frederick Libert
A1 David Brown
A1 Naima Kheddoumi
A1 Adam Shlien
A1 Tomasz Konopka
A1 Roberto Salgado
A1 Denis Larsimont
A1 Kornelia Polyak
A1 karen Willard-Gallo
A1 Christine Desmedt
A1 Martine Piccart
A1 Marc Abramowicz
A1 Peter J Campbell
A1 Christos Sotiriou
A1 Vincent Detours
YR 2014
UL http://biorxiv.org/content/early/2014/12/16/012849.abstract
AB A-to-I editing substitutes inosines for adenosines at specific positions in mRNAs and can substantially alter a cell’s transcriptome. Currently, little is known about how this type of editing functions in cancer. This study demonstrates that A-to-I edited mRNA loci are conserved not only across matched normal and tumor breast tissues but also between patients; however, the editing frequency is higher in tumor compared to normal breast tissue. We developed a model that shows the editing enzyme ADAR uniformly controls the editing frequency across all loci, proportional to each individual locus’ editability, which is a property of its surrounding nucleotide sequence. We also demonstrate that the type I interferon response and ADAR DNA copy number together determine ADAR expression in breast and potentially the vast majority of human cancers. ADAR silencing using shRNA lentivirus transduction in breast cancer cell lines led to a decrease in cell proliferation and an increase in apoptosis. Our results reveal that A-to-I editing is a pervasive but well controlled phenomenon in cancer that can profoundly influence the transcriptome and cellular functions in breast cancer.