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1.  RNA Homeostasis Governed by Cell Type-Specific and Branched Feedback Loops Acting on NMD 
Molecular cell  2011;43(6):950-961.
Nonsense-mediated mRNA decay (NMD) is a conserved RNA decay pathway that degrades aberrant mRNAs and directly regulates many normal mRNAs. This dual role for NMD raises the possibility that its magnitude is buffered to prevent the potentially catastrophic alterations in gene expression that would otherwise occur if NMD were perturbed by environmental or genetic insults. In support of this, here we report the existence of a negative feedback regulatory network that directly acts on seven NMD factors. Feedback regulation is conferred by different branches of the NMD pathway in a cell type-specific and developmentally regulated manner. We identify feedback-regulated NMD factors that are rate limiting for NMD and demonstrate that reversal of feedback regulation in response to NMD perturbation is crucial for maintaining NMD. Together, our results suggest the existence of an intricate feedback network that maintains both RNA surveillance and the homeostasis of normal gene expression in mammalian cells.
PMCID: PMC4281029  PMID: 21925383
2.  Suppressing nonsense—a surprising function for 5-azacytidine 
EMBO Molecular Medicine  2014;6(12):1518-1520.
In this issue of EMBO Molecular Medicine, Bhuvanagiri et al report on a chemical means to convert molecular junk into gold. They identify a chemical inhibitor of a quality control pathway that is best known for its ability to clear cells of rubbish, but that in certain cases can be detrimental because it eliminates “useful” garbage. The chemical inhibitor identified by Bhuvanagiri et al perturbs Nonsense-Mediated RNA Decay (NMD), a RNA surveillance pathway that targets mRNAs harboring premature termination codons (PTCs) for degradation (Kervestin & Jacobson, 2012).
PMCID: PMC4287971  PMID: 25378479
3.  Posttranscriptional Control of the Stem Cell and Neurogenic Programs by the Nonsense-Mediated RNA Decay Pathway 
Cell reports  2014;6(4):748-764.
The mechanisms dictating whether a cell proliferates or differentiates have undergone intense scrutiny but remain poorly understood. Here, we report that a central component in the nonsense-mediated RNA decay (NMD) pathway—UPF1—plays a key role in this decision by promoting the proliferative, undifferentiated cell state. UPF1 acts, in part, by destabilizing the NMD substrate encoding the TGFβ inhibitor, SMAD7, and stimulating TGFβ signaling. UPF1 also promotes the decay of mRNAs encoding many other proteins that oppose the proliferative, undifferentiated cell state. Neural differentiation is triggered when NMD is downregulated by neurally expressed microRNAs (miRNAs). This UPF1-miRNA circuitry is highly conserved and harbors negative feedback loops that act as a molecular switch. Our results suggest that the NMD RNA decay pathway collaborates with the TGF-β signaling pathway to lock-in the stem-like state, a cellular state that is stably reversed when neural differentiation signals that induce NMD-repressive miRNAs are received.
PMCID: PMC3962089  PMID: 24529710
4.  Nanolitre-scale crystallization using acoustic liquid-transfer technology 
Acoustic droplet ejection achieves precise, tipless, non-invasive transfer of diverse aqueous solutions, enabling nanolitre-scale crystallization trials. The rapid and scalable technique demonstrated successful crystal growth with diverse targets in drop volumes as small as 20 nl.
Focused acoustic energy allows accurate and precise liquid transfer on scales from picolitre to microlitre volumes. This technology was applied in protein crystallization, successfully transferring a diverse set of proteins as well as hundreds of precipitant solutions from custom and commercial crystallization screens and achieving crystallization in drop volumes as small as 20 nl. Only higher concentrations (>50%) of 2-­methyl-2,4-pentanediol (MPD) appeared to be systematically problematic in delivery. The acoustic technology was implemented in a workflow, successfully reproducing active crystallization systems and leading to the discovery of crystallization conditions for previously uncharacterized proteins. The technology offers compelling advantages in low-nanolitre crystallization trials by providing significant reagent savings and presenting seamless scalability for those crystals that require larger volume optimization experiments using the same vapor-diffusion format.
PMCID: PMC3413209  PMID: 22868754
acoustic liquid transfer; nanolitre-scale crystallization

Results 1-4 (4)