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DOI: 10.1016/j.cell.2010.02.023
¤ OpenAccess: Hybrid
This work has “Hybrid” OA status. This means it is free under an open license in a toll-access journal.

A Global In Vivo Drosophila RNAi Screen Identifies NOT3 as a Conserved Regulator of Heart Function

G. Gregory Neely,Keiji Kuba,Anthony Cammarato,Kazuya Isobe,Sabine Amann,Liyong Zhang,Mitsushige Murata,Lisa Elmén,Vaijayanti Gupta,Suchir Arora,Rinku Sarangi,Debasis Dan,Susumu Fujisawa,Takako Usami,Cui ping Xia,Alex C. Keene,Nakissa N. Alayari,Hiroyuki Yamakawa,Ulrich Elling,Christian Berger,Maria Novatchkova,Rubina Koglgruber,Keiichi Fukuda,Hiroshi Nishina,Mitsuaki Isobe,J. Andrew Pospisilik,Yumiko Imai,Arne Pfeufer,Andrew A. Hicks,Peter P. Pramstaller,Sai Subramaniam,Akinori Kimura,Karen Ocorr,Rolf Bodmer,Josef Penninger

Biology
RNA interference
Gene silencing
2010
Heart diseases are the most common causes of morbidity and death in humans. Using cardiac-specific RNAi-silencing in Drosophila, we knocked down 7061 evolutionarily conserved genes under conditions of stress. We present a first global roadmap of pathways potentially playing conserved roles in the cardiovascular system. One critical pathway identified was the CCR4-Not complex implicated in transcriptional and posttranscriptional regulatory mechanisms. Silencing of CCR4-Not components in adult Drosophila resulted in myofibrillar disarray and dilated cardiomyopathy. Heterozygous not3 knockout mice showed spontaneous impairment of cardiac contractility and increased susceptibility to heart failure. These heart defects were reversed via inhibition of HDACs, suggesting a mechanistic link to epigenetic chromatin remodeling. In humans, we show that a common NOT3 SNP correlates with altered cardiac QT intervals, a known cause of potentially lethal ventricular tachyarrhythmias. Thus, our functional genome-wide screen in Drosophila can identify candidates that directly translate into conserved mammalian genes involved in heart function.
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    A Global In Vivo Drosophila RNAi Screen Identifies NOT3 as a Conserved Regulator of Heart Function” is a paper by G. Gregory Neely Keiji Kuba Anthony Cammarato Kazuya Isobe Sabine Amann Liyong Zhang Mitsushige Murata Lisa Elmén Vaijayanti Gupta Suchir Arora Rinku Sarangi Debasis Dan Susumu Fujisawa Takako Usami Cui ping Xia Alex C. Keene Nakissa N. Alayari Hiroyuki Yamakawa Ulrich Elling Christian Berger Maria Novatchkova Rubina Koglgruber Keiichi Fukuda Hiroshi Nishina Mitsuaki Isobe J. Andrew Pospisilik Yumiko Imai Arne Pfeufer Andrew A. Hicks Peter P. Pramstaller Sai Subramaniam Akinori Kimura Karen Ocorr Rolf Bodmer Josef Penninger published in 2010. It has an Open Access status of “hybrid”. You can read and download a PDF Full Text of this paper here.