TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells.

SOLUTION: Which is the receptor for substrates of Chaperone Mediated Autophagy?

PROBLEM: Fish species are expected to shrink in size by up to 24% because of global warming, say scientists. The scientists argue that failure to control greenhouse gas emissions will have a greater effect on marine ecosystems than previously thought. Previous research has suggested that changing ocean temperatures would affect both the distribution and the reproductive abilities of many species of fish. This new work suggests that fish size would also be heavily affected. The researchers built a model to see how fish would react to lower levels of oxygen in the water. As ocean temperatures increase, so do the body temperatures of fish. But, according to lead author, Dr William Cheung, from the University of British Columbia, the lower level of oxygen in the water is key. Warmer waters could decrease ocean oxygen levels and greatly reduce fish body weight. On the other hand, rising temperatures directly increase the metabolic rate of the fish's body function. This leads to an increase in oxygen demand for normal body activities. So the fish will run out of oxygen for growth at a smaller body size. The research team also used its model to predict fish movements as a result of warming waters. The group believes that most fish populations will move towards the Earth's poles at a rate of up to 35km per decade. "So in, say, the North Sea," says Dr Cheung," one would expect to see more smaller-body fish from tropical waters in the future." Taking these factors into consideration, the research team concludes that fish body size will shrink between 14% and 24%, with the largest decreases in the Indian and Atlantic oceans. When compared with actual observations of fish sizes, the model seems to _ what's actually happening in the seas. The researchers looked at two case studies involving North Atlantic cod and haddock. They found that recorded data on these fish showed greater decreases in body size than the models had predicted. Dr Alan Baudron, from the University of Aberdeen, UK, believes smaller-sized fish could seriously affect the ability of fish to reproduce. "Smaller fish produce fewer and smaller eggs which could affect the reproductive potential of fish stocks," he said.

SOLUTION: What is the key factor making the fish smaller now?

PROBLEM: In plant, primary transcripts (pri-miRNAs) transcribed from miRNA genes by RNA polymerase II are first processed into stem-loop pre-miRNAs and further chopped into 21nt long miRNAs by RNase III-like enzyme DCL1. SERRATE (SE) protein is an essential component for miRNA processing by assisting DCL1 for accurate cleavage. Here we report the crystal structure of Arabidopsis SE core (residues 194-543) at 2.7A. SE core adopts the 'walking man-like' topology with N-terminal helices, C-terminal non-canonical zinc-finger domain and novel Middle domain resembling the leading leg, the lagging leg and the body, respectively. Pull-down assay shows that SE core provides the platform for HYL1 and DCL1 binding, whereas in vitro RNA binding and in vivo mutant rescue experiments suggest that the non-canonical zinc-finger domain coupled with C-terminal tail binds miRNA precursors. SE presumably works as a scaffold-like protein capable of binding both protein and RNA to guide the positioning of miRNA precursor toward DCL1 catalytic site within miRNA processing machinery in plant.

SOLUTION:
Which polymerase transcribes pri-miRNAs?