RNA: Networks & Imaging

Abstract

The past few years have brought about a fundamental change in our understanding and definition of the RNA world and its role in the functional and regulatory architecture of the cell. The discovery of small RNAs that regulate many aspects of differentiation and development have joined the already known non-coding RNAs that are involved in chromosome dosage compensation, imprinting, and other functions to become key players in regulating the flow of genetic information. It is also evident that there are tens or even hundreds of thousands of other non-coding RNAs that are transcribed from the mammalian genome, as well as many other yet-to-be-discovered small regulatory RNAs. In the recent symposium RNA: Networks & Imaging held in Heidelberg, the dual roles of RNA as a messenger and a regulator in the flow of genetic information were discussed and new molecular genetic and imaging methods to study RNA presented.

Figure 1

Regulatory ‘feedback' and ‘feed-forward' networks involving ncRNAs. ncRNAs are involved in the regulation of gene expression at different levels including the control of chromatin structure, RNA transcription and processing, mRNA stability and translational activity, and self-regulation (adapted from Mattick, 2003).

Figure 2

Schematics illustrating two strategies to map genetic interactions based on RNAi. The top panel illustrates the ‘guilt-by-association' principle: if the knockdown of gene x in a wild-type background causes a specific phenotype that is different from the one caused in an already mutated (e.g. gene y) background, then these two genes (e.g. genes x and y) must genetically interact. Another strategy is based on causing a distinct phenotype by knocking down a specific gene. Additional knockdowns are then performed, which may either rescue or enhance the phenotype seen after the first genetic knockdown. Both results indicate genetic interactions between the genes that have been knocked down (bottom panel).

Figure 3

Schematics illustrating two models on RNA transcription with either a mobile or static RNA polymerase. Considering a fully mobile RNA polymerase that translocates and rotates (top panel), the nascent transcript would entwine about the template, and some mechanism would have to be found to untwine the tangle to allow the transcript to escape to the cytoplasm. The untwining problem can be eliminated if the DNA both translocates and rotates while the polymerase is essentially immobile because of its clustering in transcription factories (bottom panel).