The Fuzzy Logic of MicroRNA Regulation: A Key to Control Cell Complexity
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Andrea Ripoli*,1, Giuseppe Rainaldi2,3, Milena Rizzo2, Alberto Mercatanti2 and Letizia Pitto2
- چاپ و سال / کشور: 2010
Description
Genomic and clinical evidence suggest a major role of microRNAs (miRNAs) in the regulatory mechanisms of gene expression, with a clear impact on development and physiology; miRNAs are a class of endogenous 22-25 nt singlestranded RNA molecules, that negatively regulate gene expression post-transcriptionally, by imperfect base pairing with the 3’ UTR of the corresponding mRNA target. Because of this imperfection, each miRNA can bind multiple targets, and multiple miRNAs can bind the same mRNA target; although digital, the miRNAs control mechanism is characterized by an imprecise action, naturally understandable in the theoretical framework of fuzzy logic. A major practical application of fuzzy logic is represented by the design and the realization of efficient and robust control systems, even when the processes to be controlled show chaotic, deterministic as well unpredictable, behaviours. The vagueness of miRNA action, when considered together with the controlled and chaotic gene expression, is a hint of a cellular fuzzy control system. As a demonstration of the possibility and the effectiveness of miRNA based fuzzy mechanism, a fuzzy cognitive map -a mathematical formalism combining neural network and fuzzy logic- has been developed to study the apoptosis/ proliferation control performed by the miRNA-17-92 cluster/E2F1/cMYC circuitry. When experimentally demonstrated, the concept of fuzzy control could modify the way we analyse and model gene expression, with a possible impact on the way we imagine and design therapeutic intervention based on miRNA silencing.
Current Genomics, 2010, 11, 350-353 Received on: April 22, 2010 - Revised on: May 18, 2010 - Accepted on: May 27, 2010
