  When small RNAs are loaded onto Argonaute proteins they can form the
RNA-induced silencing complexes (RISCs), which mediate RNA interference.
RISC-formation is dependent on a shared pool of Argonaute proteins and RISC
loading factors, and is thus susceptible to competition among small RNAs for
loading. We present a mathematical model that aims to understand how small RNA
competition for the PTR resources affects target gene repression. We discuss
that small RNA activity is limited by RISC-formation, RISC-degradation and the
availability of Argonautes. Together, these observations explain a number of
PTR saturation effects encountered experimentally. We show that different
competition conditions for RISC-loading result in different signatures of PTR
activity determined also by the amount of RISC-recycling taking place. In
particular, we find that the small RNAs less efficient at RISC-formation, using
fewer resources of the PTR pathway, can perform in the low RISC-recycling range
equally well as their more effective counterparts. Additionally, we predict a
novel signature of PTR in target expression levels. Under conditions of low
RISC-loading efficiency and high RISC-recycling, the variation in target levels
increases linearly with the target transcription rate. Furthermore, we show
that RISC-recycling determines the effect that Argonaute scarcity conditions
have on target expression variation. Our observations taken together offer a
framework of predictions which can be used in order to infer from experimental
data the particular characteristics of underlying PTR activity.
