Compound C inhibits nonsense-mediated RNA decay independently of AMPK

The nonsense mediated RNA decay (NMD) pathway safeguards the integrity of the transcriptome by targeting mRNAs with premature translation termination codons (PTCs) for degradation. It also regulates gene expression by degrading a large number of non-mutant RNAs (including mRNAs and noncoding RNAs) that bear NMD-inducing features. Consequently, NMD has been shown to influence development, cellular response to stress, and clinical outcome of many genetic diseases. Small molecules that can modulate NMD activity provide critical tools for understanding the mechanism and physiological functions of NMD, and they also offer potential means for treating certain genetic diseases and cancer. Therefore, there is an intense interest in identifying small-molecule NMD inhibitors or enhancers. It was previously reported that both inhibition of NMD and treatment with the AMPK-selective inhibitor Compound C (CC) induce autophagy in human cells, raising the possibility that CC may be capable of inhibiting NMD. Here we show that CC indeed has a NMD-inhibitory activity. Inhibition of NMD by CC is, however, independent of AMPK activity. As a competitive ATP analog, CC does not affect the kinase activity of SMG1, an essential NMD factor and the only known kinase in the NMD pathway. However, CC treatment down-regulates the protein levels of several NMD factors. The induction of autophagy by CC treatment is independent of ATF4, a NMD target that has been shown to promote autophagy in response to NMD inhibition. Our results reveal a new activity of CC as a NMD inhibitor, which has implications for its use in basic research and drug development

Analysing GCN4 Translational Control in Yeast by Stochastic Chemical Kinetics Modelling and Simulation

Peer reviewedPublisher PD

Effects of infill walls and floor diaphragms on the dynamic characteristics of a narrow-rectangle building

This is the peer reviewed version of the following article: Pan, T.-C., You, X. and Brownjohn, J. M. W. (2006), Effects of infill walls and floor diaphragms on the dynamic characteristics of a narrow-rectangle building. Earthquake Engineering and Structural Dynamics, 35: 637–651. .which has been published in final form at: doi:10.1002/eqe.550Most buildings in Singapore are lightly reinforced concrete structures which are manly designed for gravity loading only, because Singapore is an island country located in a low to moderate seismic region. The dynamic properties of a typical high-rise residential building with a long, narrow rectangular floor plan are studied using both experimental and numerical methods. The effects of the brick infill walls and the flexible diaphragms on the dynamic characteristics of the building are discussed in detail. The results from the ambient vibration tests are correlated with the numerical results of three different finite element models with different levels of sophistication. They include a bare frame model, a frame model with brick infill walls, and a frame model with both brick infill walls and flexible diaphragms. The dynamic properties of the third model match very well with the measured results in terms of both the natural frequencies and the mode shapes. The correlation results demonstrate the respective effects of the brick infill walls and the flexible diaphragms on the dynamic characteristics of the narrow-rectangle building structure

The Role of HNRNPC-RARG in APL-like AML

https://openworks.mdanderson.org/sumexp22/1037/thumbnail.jp