RT Journal Article
SR Electronic
T1 Genome-wide co-localization of RNA-DNA interactions and fusion RNA pairs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 472019
DO 10.1101/472019
A1 Zhangming Yan
A1 Norman Huang
A1 Weixin Wu
A1 Weizhong Chen
A1 Yiqun Jiang
A1 Jingyao Chen
A1 Xuerui Huang
A1 Xingzhao Wen
A1 Jie Xu
A1 Qiushi Jin
A1 Kang Zhang
A1 Zhen Chen
A1 Shu Chien
A1 Sheng Zhong
YR 2018
UL http://biorxiv.org/content/early/2018/11/20/472019.abstract
AB Fusion transcripts are used as biomarkers in companion diagnoses. Although more than 15,000 fusion RNAs have been identified from diverse cancer types, few common features have been reported. Here, we compared 16,410 fusion transcripts detected in cancer (from a published cohort of 9,966 tumor samples of 33 cancer types) with genome-wide RNA-DNA interactions mapped in two normal, non-cancerous cell types (using iMARGI, an enhanced version of the MARGI [Mapping RNA-Genome Interactions assay]). Among the top 10 most significant RNA-DNA interactions in normal cells, 5 co-localized with the gene pairs that formed fusion RNAs in cancer. Furthermore, throughout the genome, the frequency of a gene pair to exhibit RNA-DNA interactions is positively correlated with the probability of this gene pair to present documented fusion transcripts in cancer. To test whether RNA-DNA interactions in normal cells are predictive of fusion RNAs, we analyzed these in a validation cohort of 96 lung cancer samples using RNA-seq. 37 out of 42 fusion transcripts in the validation cohort were found to exhibit RNA-DNA interactions in normal cells. Finally, by combining RNA-seq, single-molecule RNA FISH, and DNA FISH, we detected a cancer sample with EML4-ALK fusion RNA without forming the EML4-ALK fusion gene. Collectively, these data suggest a novel RNA-poise model, where spatial proximity of RNA and DNA could poise for the creation of fusion transcripts.Author contributionsConceptualization, Z.Y, N.H., and S.Z.; Methodology, Z.Y, N.H., W.W., and W.C.; Investigation, Z.Y, N.H., W.W., W.C., YJ., J.C., X.H., Z.C., K.Z., S.C., and S.Z.; Writing – Original Draft, Z.Y, N.H. W.W., and S.Z.; Writing – Review & Editing, Z.Y, Z.C., S.C., and S.Z.; Funding Acquisition, S.C. and S.Z.; Resources, K.Z. and S.Z.; Supervision, S.C. and S.Z.S.Z. is a co-founder of Genemo, Inc., which does not have financial interests with this work. The authors have no financial interests to declare.