RNAi screen indicates widespread biological function for human natural antisense transcripts.
Natural antisense transcripts represent a class of regulatory RNA molecules, which are characterized by their complementary sequence to another RNA transcript. Extensive sequencing efforts suggest that natural antisense transcripts are prevalent throughout the mammalian genome; however, their biological significance has not been well defined. We performed a loss-of-function RNA interference (RNAi) screen, which targeted 797 evolutionary conserved antisense transcripts, and found evidence for a regulatory role for a number of natural antisense transcripts. Specifically, we found that natural antisense transcripts for CCPG1 and RAPGEF3 may functionally disrupt signaling pathways and corresponding biological phenotypes, such as cell viability, either independently or in parallel with the corresponding sense transcript. Our results show that the large-scale siRNA screen can be applied to evaluate natural antisense transcript modulation of fundamental cellular events.
Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida, United States of America.
Mohammad Ali
MA
Faghihi
Jannet
J
Kocerha
Farzaneh
F
Modarresi
Pär G
PG
Engström
Alistair M
AM
Chalk
Shaun P
SP
Brothers
Eric
E
Koesema
Georges
G
St Laurent
Claes
C
Wahlestedt
D002460:Cell Line; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
D016372:RNA, Antisense; D012333:RNA, Messenger