title: From mobility to crosstalk. A model of intracellular miRNAs motion may explain the RNAs interaction mechanism on the basis of target subcellular localization.
abstract: MicroRNAs (miRNAs), 22 nucleotides long molecules with the function to reduce gene expression by inhibiting mRNA translation through partial complementary to one or more messenger RNA (mRNA) molecules. A single miRNA can reduce the expression levels of hundreds of genes and one mRNA can be a target for many miRNAs. Despite the study models used so far, miRNAs and mRNAs cannot be seen as acting in an isolated manner or even "in pairs". They most likely exert their complex actions through numerous overlapping interrelations. One of the models depicting interdependence of intracytoplasmic RNAs is the crosstalk model. It is based on a competition between several target mRNAs which are regulated by the same miRNA. In this paper, we will discuss the mobility mechanism of miRNAs, recently suggested by data from "single particle tracking" experiments. These data suggests that miRNA intracellular mobility may be of "intermittent active transport"(IAT) type. IAT is a mobility model composed by alternation of active transport (AT) and Brownian motion (BM). Based on a mathematical model, we concluded that, AT phase may explain the efficiency in reaching far targets and the BM phase may explain the competition. Furthermore, we suggest that the interaction between miRNAs and their targets depends on the concentration of the molecules, the affinity between the molecules and also on the intracellular localization of the molecules. Hence, the probability that a miRNA interacts with its target depends also on the distance to the target and the macromolecular crowding. Taken together, our data proposes an intracytoplasmic mobility mechanism for miRNA and shows that this model can partially explain the RNA crosstalk.
authors: Department of Surgery, Fundeni Clinical Hospital, 258 Fundeni Street, Bucharest, 22328, Romania; "Carol Davila" University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, Bucharest 050474, Romania. Electronic address: catvasilescu@gmail.com.
authors: Catalin
authors: C
authors: Vasilescu
authors: University Politehnica of Bucharest, Splaiul Independenei 313, Bucharest, 060042, Romania.
authors: Mihai
authors: M
authors: Tanase
authors: "Carol Davila" University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, Bucharest 050474, Romania.
authors: Mihnea
authors: M
authors: Dragomir
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The Center for RNA Interference and Non-coding RNAs, The University of Texas, MD Anderson Cancer Center, So Campus Research Bldg 3 (3SCR4.3424), 1881 East Road, Unit 1950, Houston 77030, TX, USA.
authors: George A
authors: GA
authors: Calin
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D008962:Models, Theoretical
chemical_list: D035683:MicroRNAs
keywords: Intermittent active transport; Intracellular transport; MiRNA competition; MiRNA mobility; MicroRNA