RT Journal Article
SR Electronic
T1 A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 434647
DO 10.1101/434647
A1 Jing Zhang
A1 Samuel E. Harvey
A1 Chonghui Cheng
YR 2018
UL http://biorxiv.org/content/early/2018/10/03/434647.abstract
AB RNA secondary structures have been increasingly recognized to play an important regulatory role in post-transcriptional gene regulation. We recently showed that RNA G-quadruplexes, which serve as cis-elements to recruit splicing factors, play a critical role in regulating alternative splicing during the epithelial-mesenchymal transition. In this study, we performed a high-throughput screen using a dual-color splicing reporter to identify chemical compounds capable of regulating G-quadruplex-dependent alternative splicing. We identify emetine and its analog cephaeline as small molecules that disrupt RNA G-quadruplexes, resulting in inhibition of G-quadruplex-dependent alternative splicing. Transcriptome analysis reveals that emetine globally regulates alternative splicing, including splicing of variable exons that contain splice site-proximal G-quadruplexes. These data suggest the use of emetine and cephaeline for investigating mechanisms of G-quadruplex-associated alternative splicing.