的转录后调节.pptVIP

Post-trancriptional Regulation by microRNA’s Herbert Levine Center for Theoretical Biological Physics, UCSD with: E. Levine, P. Mchale, and E. Ben Jacob (Tel-Aviv) Outline: Introduction Basic model Spatial sharpening Temporal Sequencing What are MicroRNA’s? MicroRNA’s (miRNA’s) are small noncoding RNA molecules that regulate eukaryotic gene expression at the translation level MicroRNA formation This talk Basic molecular model Local vs global parameters Spatial sharpening Temporal control Basic silencing model Basic silencing model II Results Threshold Effect Cartoon vs Reality Local vs. Global parameters Data on silencing has been very controversial, with disagreements as to whether there is both mRNA and protein repression or only protein repression In our model, the repression ratio can be altered by cell state (global) variables such as the transport into and out of the processed state, and miRNA loss (q) Local vs. Global parameters Local vs. Global parameters Different protocols can give opposite answers if these are not carefully controlled Simple physics but complex biology Spatial sharpening What happens if we have a miRNA expressed with the opposite spatial pattern from its target mRNA? Motivation: Complementary expression patterns And, the miRNA might diffuse from cell to cell Motivation - intercellular transport of siRNA in plants Could this be an actively maintained front with q0? Conceptual idea Spatial model Note - eq has been rescaled using We will assume that the transcription profiles are 1d functions, decaying in opposite directions, and investigate what are the resultant mRNA and miRNA The relevant parameters are the annihilation rate k and the miRNA diffusion constant D (compared to the scale established by transcription) Zero diffusion, large k Adding miRNA diffusion K=10000 Dark line is analytic calculation Interface is sharpened Crossing point is shifted to left Effect of increasing rate k A