23 research outputs found
What do cross-country surveys tell us about social capital?
We validate survey measures of social capital with a new behavioral data set that examines whether citizens report a lost wallet to its owner. Using data from more than 17,000 lost wallets across 40 countries, we find that survey measures of social capital — especially questions concerning generalized trust or generalized morality — are strongly and significantly correlated with country-level differences in wallet reporting rates. A second finding is that lost wallet reporting rates predict unique variation in the outputs of social capital, such as economic development and government effectiveness, not captured by existing measures
Trying to make sense in nonsense-mediated mRNA decay
Despite over 30 years of research, the molecular mechanisms of nonsense-mediated mRNA decay (NMD) are still not well understood. NMD appears to exist in most eukaryotes and is intensively studied in S. cerevisiae, C. elegans, D. melanogaster and in mammalian cells. Current evidence suggests that the core of NMD – involving UPF1, UPF2 and UPF3 – is evolutionarily conserved, but that different species may have evolved slightly different ways to identify target mRNAs for NMD and to degrade them.
Our lab has shown that the exon junction complex (EJC) is not absolutely required for NMD in human cells (Bühler et al., NSMB 2006) and that it is neither restricted to CBP80-bound mRNAs as classical models claim (Rufener & Mühlemann, NSMB 2013). Together with the finding that long 3’ UTRs often are an NMD-inducing feature (Eberle et al, PLoS Biol 2008; Yepiskoposyan et al., RNA 2011), our data is consistent with much of the data from other species and hence has led to a “unified” working model for NMD (Stalder & Mühlemann, Trends Cell Biol 2008; Schweingruber et al., Biochim Biophys Acta 2013).
Our recent iCLIP experiments with endogenous UPF1 indicate that UPF1 binds mRNAs indiscriminately with respect to being an NMD target or not before they engage with ribosomes (Zünd et al., NSMB 2013). After onset of translation, UPF1 is cleared from the coding region but remains bound to the 3’ UTR of mRNAs. Why this 3’ UTR-associated in some cases induces NMD and in others not is currently being investigated and not yet understood. Following assembly of a phospho-UPF1-containing NMD complex, decay adaptors (SMG5, SMG7, PNRC2) and/or the endonuclease SMG6 are recruited. While the latter cleaves the mRNA in the vicinity of the termination codon, the former proteins induce deadenylation, decapping and exonucleolytic degradation of the mRNA.
In my talk, I will give an overview about the latest developments in NMD – with a focus on our own work – and try to integrate the bits and pieces into a somewhat coherent working model
Individual-nucleotide-resolution UV Cross-linking and Immunoprecipitation (iCLIP) of UPF1
UPF1 RNA Immunoprecipitation from Mini-μ Construct–expressing Cells
UPF1, an RNA helicase and a core factor of nonsense-mediated mRNA decay (NMD), interacts with RNA independently of the sequence context. To investigate the influence of translation on the association of UPF1 with specific reporter transcripts, UPF1 RNA immunoprecipitations (RIPs) are performed from Hela cells that either express a normally translated immunoglobulin-µ (Ig-µ) reporter (mini µ) or a version with a stable stem loop in the 5' UTR (SL mini µ) that efficiently inhibit translation initiation (Zund et al., 2013). Both the cloning of the SL mini µ reporter construct and the UPF1 RIP experiment are described in detail
Recent transcriptome-wide mapping of UPF1 binding sites reveals evidence for its recruitment to mRNA before translation
The ATP-dependent RNA helicase UPF1, a key factor in nonsense-mediated mRNA decay (NMD), was so far thought to be recruited specifically to NMD-targeted mRNAs by aberrantly terminating ribosomes. However, two recent publications reporting independently transcriptome-wide mapping of UPF1 occupancy on RNA challenge this model and instead provide evidence that UPF1 binds to mRNA already before translation. According to the new data, UPF1 appears to initially bind all mRNAs along their entire length and gets subsequently stripped off the coding sequence by translating ribosomes. This re-poses the question of where and how UPF1 engages with mRNA and how the NMD-targeted transcripts are selected among the UPF1-bound mRNAs
What do cross-country surveys tell us about social capital?
We assess the predictive power of survey measures of social capital with a new behavioral data set that examines whether citizens report a lost wallet to its owner. Using data from more than 17,000 “lost” wallets across 40 countries, we find that survey measures of social capital—especially questions concerning generalized trust or generalized morality — are strongly and significantly correlated with country-level differences in wallet reporting rates. A second finding is that lost wallet reporting rates predict unique variation in the outputs of social capital, such as economic development and government effectiveness, not captured by existing measures
Civic honesty around the globe
Civic honesty is essential to social capital and economic development but is often in conflict with material self-interest. We examine the trade-off between honesty and self-interest using field experiments in 355 cities spanning 40 countries around the globe. In these experiments, we turned in more than 17,000 lost wallets containing varying amounts of money at public and private institutions and measured whether recipients contacted the owners to return the wallets. In virtually all countries, citizens were more likely to return wallets that contained more money. Neither nonexperts nor professional economists were able to predict this result. Additional data suggest that our main findings can be explained by a combination of altruistic concerns and an aversion to viewing oneself as a thief, both of which increase with the material benefits of dishonesty