Novel functional small RNAs are selectively loaded onto mammalian Ago1.

Argonaute (Ago) proteins function in RNA silencing as components of the RNA-induced silencing complex (RISC). In lower organisms, the small interfering RNA and miRNA pathways diverge due in part to sorting mechanisms that direct distinct small RNA (sRNA) duplexes onto specific Ago-RISCs. However, such sorting mechanisms appear to be lost in mammals. miRNAs appear not to distinguish among Ago1-4. To determine the effect of viral infection on the sorting system, we compared the content of deep-sequenced RNA extracted from immunoprecipitation experiments with the Ago1 and Ago2 proteins using Epstein-Barr virus (EBV)-infected cells. Consistent with previous observations, sequence tags derived from miRNA loci in EBV and humans globally associate in approximately equivalent amounts with Ago1 and Ago2. Interestingly, additional sRNAs, which have not been registered as miRNAs, were associated with Ago1. Among them, some unique sequence tags derived from tandem loci in the human genome associate exclusively with Ago1 but not, or rarely, with Ago2. This is supported by the observation that the expression of the unique sRNAs in the cells is highly dependent on Ago1 proteins. When we knocked down Ago1, the expression of the Ago1-specific sRNAs decreased dramatically. Most importantly, the Ago1-specific sRNAs bound to mRNAs and regulated target genes and were dramatically upregulated, depending on the EBV life cycle. Therefore, even in mammals, the sorting mechanism in the Ago1-4 family is functional. Moreover, the existence of Ago1-specific sRNAs implies vital roles in some aspects of mammalian biology.

Local structure and dynamics of benzene confined in the IRMOF-1 nanocavity as studied by molecular dynamics simulation.

The local structure and dynamic behaviour of a benzene molecular assembly confined within the nano-cavities of a zinc-based metal-organic framework, [Zn(4)O(CO(2)C(6)H(4)CO(2))(3)](n) (IRMOF-1), were investigated by means of molecular dynamics (MD) simulations. The local structure of the confined benzene molecules was evaluated using radial distribution functions. The sites for adsorption of benzene in IRMOF-1 were well defined by the simulation. The diffusion coefficients at ambient temperature suggested that the mobility of the confined benzene was high, comparable to the bulk fluid. Decreasing the temperature gave rise to the aggregation of benzene in the IRMOF-1 frameworks. Molecular aggregation was attributed to the localization of benzene in the large and the small cavities of IRMOF-1, respectively. Both the translational diffusion coefficient and the trajectory of benzene provided evidence that the localization of benzene in the large and the small cavities takes place at ca. 200 K. Furthermore, at high benzene loading, the migration of benzene in the small cavities was prevented (frozen) below 135 K. Thus, the translational degree of freedom of the benzene molecules changed drastically, depending on the temperature.