The role of incoherent microRNA-mediated feedforward loops in noise buffering

by Michele Caselle

Tuesday 24 May 2011, 15:00 → 17:00 Europe/Rome

Aula 7 (Dip. di Fisica - Edificio E. Fermi)

MicroRNAs are endogenous non-coding RNAs which negatively regulate the expression of protein-coding genes in plants and animals. They are known to play an important role in several biological processes and, together with transcription factors, form a complex and highly interconnected regulatory network. Looking at the structure of this network, it is possible to recognize a few overrepresented motifs which are expected to perform important elementary regulatory functions. Among them, a special role is played by the microRNA-mediated feedforward loop in which a master transcription factor regulates a microRNA ! and, together with it, a set of target genes. We show analytically and through simulations that the incoherent version of this motif can couple the fine-tuning of a target protein level with an efficient noise control, thus conferring precision and stability to the overall gene expression program, especially in the presence of fluctuations in upstream regulators. The optimal attenuation of fluctuations coincides with a modest repression of the target expression. This feature is coherent with the expected fine-tuning function and in agreement with experimental observations. As an example of our results we discuss in detail the miRNA mediated FFLs involving Myc as master Transcription factor.