RNAi Screen Indicates Widespread Biological Function for Human Natural Antisense Transcripts

PLoS One

Pär G. Engström¹  Georges St. Laurent III²  Eric Koesema³  Mohammad Ali Faghihi⁴  Jannet Kocerha⁴  Shaun P. Brothers⁴  Farzaneh Modarresi⁴  Claes Wahlestedt⁵  Alistair M. Chalk⁶ 

[1] Bioinformatics Institute, Hinxton, Cambridge, United Kingdom;Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America;Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida, United States of America;Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida, United States of America;Immunovirology-Biogenisis Group, University of Antioquia, Medellin, Colombia;National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Australia

关键词: Small interfering RNAs;    Antisense RNA;    Non-coding RNA;    Luciferase;    Cell cycle and cell division;    Microarrays;    Cell proliferation;    RNA interference;   

DOI  :  10.1371/journal.pone.0013177

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY