Post-transcriptional Regulation Technologies - Erin Zwack

Overview:

Regulation of translation provides an excellent tool for research on metabolic and other pathways in organisms, and for the production of different sensors by controlling the translation of specific genes depending on cellular conditions. Further development of these types of technology could provide a “knock-down” equivalent to RNAi available in some eukaryotes. A gene of interest could be expressed normally at all times when the regulator is not active; thus, no ill effects will result before the pathway activates if the gene has another purpose as well. Other sythetic biologists could use these technologies to engineer fast-responding, RNA-based biological sensors for environmental chemicals, or novel pathways.

Development of Systems

In most cases, post-transcriptional regulatory mechanisms that were developed and worked in eukaryotes cannot be directly transferred to prokaryotes. Modifications are necessary because eukaryotic and prokaryotic transcription and translation do not follow the exact same path (figure 1). File:Eukarotictt.gif In eukaryotes, mRNA must have introns spliced out before translation begins; thus, any mechanism that regulates translation has time to bind or manipulate the mRNA. In prokaryotes, translation begins as soon as the ribosomal binding site is transcribed and accessible to a ribosome.

Prokaryotes:

Isaacs FJ, et al. Engineered riboregulators enable post-transcriptional control of gene expression. Nat Biotechnol. (2004) 22:841-47.

Dr. Gallivan's work on synthetic riboswitches

Eukaryotes:

Bayer TS and Smolke CD. Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat Biotechnol. (2005) 3:337-43.