RNA binding proteins (RBPs) are vital to the regulation of mRNA transcripts, and can alter mRNA localization, degradation, translation, and storage. Whi3 was originally identified in a screen for small cell size mutants, and has since been characterized as an RBP. The identification of Whi3-interacting mRNAs involved in mediating cellular responses to stress suggested that Whi3 might be involved in stress-responsive RNA processing. We show that Whi3 localizes to stress granules in response to glucose deprivation or heat shock. The kinetics and pattern of Whi3 localization in response to a range of temperatures were subtly but distinctly different from those of known components of RNA processing granules. Deletion of Whi3 resulted in an increase in the relative abundance of Whi3 target RNAs, either in the presence or absence of heat shock. Increased levels of the CLN3 mRNA in whi3Δ cells may explain their decreased cell size. Another mRNA target of Whi3 encodes the zinc-responsive transcription factor Zap1, suggesting a role for Whi3 in response to zinc stress. Indeed, we found that whi3Δ cells have enhanced sensitivity to zinc toxicity. Together our results suggest an expanded model for Whi3 function: in addition to its role as a regulator of the cell cycle, Whi3 may have a role in stress-dependent RNA processing and responses to a variety of stress conditions.
Cardiovascular mortality for end-stage renal disease (ESRD) patients is about 30 times the risk in the general population. About 30% of ESRD patients have hyperlipidemia. The 1998 National Kidney Foundation Task Force on Cardiovascular Disease recommends implementation of effective measures to prevent and treat cardiovascular disease in this population. Our intent was to evaluate the extent of use of cardioprotective drugs in ESRD patients through a quality improvement project. Twenty-eight dialysis facilities throughout Ohio volunteered for this project. Data regarding use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) in heart failure, beta-blockers in myocardial infarction (MI), aspirin in coronary artery disease, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) were collected using chart abstraction for the period March through May 2000. The results were compared to Ohio hospital discharges from July through September 2000. This latter population was comprised of non--ESRD patients. Dialysis facilities were visited and interviews were conducted with staff members. Information was gathered regarding facility infrastructure, quality improvement process, and existing protocols. 27% of ESRD patients with a history of heart failure were on ACE-I, compared to 75.7% of non-ESRD patients. 34.8% of ESRD patients with a previous MI were taking beta-blockers, compared with 68.0% of non-ESRD patients with a prior MI. Aspirin use in ESRD patients with a previous MI was 52.8%, compared to 88% in non-ESRD patients with a prior MI. 17.3% of ESRD patients were on statins. Hyperlipidemia is found in 30% to 50% of ESRD patients. The use of cardioprotective drugs in the Medicare ESRD patient is lower than in the Medicare non-dialysis counterpart. Reasons for this are related to fragmentation of health care arising from communication and infrastructure issues. Until these issues are addressed and resolved, efforts at initiation of cardioprotective strategies will be slowed.
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