Knocking Down Genes for Fun and Function

Reprinted with permission from Nature  PROTEIN SILENCING: Silencing of nuclear envelope proteins lamin A/C siRNA duplex (a,d) with GL2 luciferase siRNA duplex (nonspecific siRNA control) (b), and with buffer only (c). Staining with lamin A/C specific antibody (a,c); staining with NuMA-specific antibody (d). Data derived from the Science Watch/Hot Papers database and the Web of Science (ISI, Philadelphia) show that Hot Papers are cited 50 to 100 times more often than the average paper of t

Written byMyrna Watanabe
| 6 min read

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Scientists once thought of eukaryotic RNA as solely active in transcription as messenger RNA (mRNA), and in translation as transfer RNA (tRNA). After Fire and colleagues first reported that double-stranded RNA (dsRNA) can interfere with gene expression,1 the conception of how gene transcription works was knocked on its head. Suddenly, these pieces of RNA, which appeared to be cellular detritus sliced out of mRNA, took on importance: They could have a role in gene suppression.

Subsequent papers by many groups, including these two Hot Papers by Thomas Tuschl and colleagues,2,3 formerly of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, are clarifying how the naturally occurring method of RNA inhibition works and how engineered small inhibitory RNAs (siRNAs) can be introduced into a cell to knock down, or suppress, specific gene expression. Barely five years since the concept was first published, researchers are looking to use siRNAs clinically.

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