Translation termination depends on the sequential ribosomal entry of eRF1 and eRF3.

Translation termination requires eRF1 and eRF3 for polypeptide-and tRNA-release on stop codons. Additionally, Dbp5/DDX19 and Rli1/ABCE1 are required; however, their function in this process is currently unknown. Using a combination of in vivo and in vitro experiments, we show that they regulate a stepwise assembly of the termination complex. Rli1 and eRF3-GDP associate with the ribosome first. Subsequently, Dbp5-ATP delivers eRF1 to the stop codon and in this way prevents a premature access of eRF3. Dbp5 dissociates upon placing eRF1 through ATP-hydrolysis. This in turn enables eRF1 to contact eRF3, as the binding of Dbp5 and eRF3 to eRF1 is mutually exclusive. Defects in the Dbp5-guided eRF1 delivery lead to premature contact and premature dissociation of eRF1 and eRF3 from the ribosome and to subsequent stop codon readthrough. Thus, the stepwise Dbp5-controlled termination complex assembly is essential for regular translation termination events. Our data furthermore suggest a possible role of Dbp5/DDX19 in alternative translation termination events, such as during stress response or in developmental processes, which classifies the helicase as a potential drug target for nonsense suppression therapy to treat cancer and neurodegenerative diseases

Transport mechanisms for synoptic, seasonal and interannual SF₆ variations and "age" of air in troposphere

We use an atmospheric general circulation model (AGCM) driven chemistry-transport model (ACTM) to simulate the evolution of sulfur hexafluoride (SF6) in the troposphere. The model results are compared with continuous measurements at 6 sites over 71° N–90° S. These comparisons demonstrate that the ACTM simulations lie within the measurement uncertainty over the analysis period (1999–2006) and capture salient features of synoptic, seasonal and interannual SF6 variability. To understand transport timescales of SF6 within the troposphere, transport times of air parcels from the surface to different regions of the troposphere ("age") are estimated from a simulation of an idealized tracer. The age estimation error and its sensitivity to the selection of reanalysis meteorology for ACTM nudging or the tracer transport by deep cumulus convection as represented in the model are discussed. Monthly-mean, 2-box model exchange times (τex) are calculated from both the observed and simulated SF6 time series at the 6 observing sites and show favorable agreement, suggesting that the ACTM adequately represents large-scale interhemispheric transport. The simulated SF6 variability is further investigated through decomposition of the mixing ratio time-tendency into advective, convective, and vertical diffusive components. The transport component analysis illustrates the role of each process in SF6 synoptic variability at the site level and provides insight into the seasonality of τex