Several of these occur in genes whose overexpression has been linked to poor cancer prognosis.ĭeep sequencing of RNAs in post-splicing, pre-translational mRNPs provides a means to identify and quantify splicing events without the confounding influence of differential mRNA decay. We identify thousands of previously unannotated splicing events while many can be attributed to splicing noise, others are evolutionarily conserved events that produce new AS-NMD isoforms likely involved in maintenance of protein homeostasis. Our RIPiT-Seq also definitively demonstrates that the splicing machinery itself has no ability to detect reading frame. Consistent with expectation, the flux through known AS-NMD pathways is substantially higher than that captured by RNA-Seq. Here we compare exon junction complex RIPiT-Seq to whole cell RNA-Seq data from HEK293 cells. RNA immunoprecipitation in tandem (RIPiT) of exon junction complex components allows for purification of post-splicing mRNA-protein particles (mRNPs) not yet subject to translation (pre-translational mRNPs) and, therefore, translation-dependent mRNA decay. Indeed, some mRNA isoforms with extremely short half-lives, such as those subject to translation-dependent nonsense-mediated decay (AS-NMD), may be completely overlooked in even the most extensive RNA-Seq analyses. The flux through competing splicing pathways cannot be determined by traditional RNA-Seq, however, because different mRNA isoforms can have widely differing decay rates. Waters, M.D.Alternative splicing, which generates multiple mRNA isoforms from single genes, is crucial for the regulation of eukaryotic gene expression. Twenty-nine percent of the cocaine users died in the hospital, which was almost twice the death rate of the non-cocaine users.Ĭo-authors of the study include: Cynthia L. Hypertension had been diagnosed in 79 percent of the cocaine users, 71 percent had documented left ventricular hypertrophy (thickening of the heart wall), and at least 64 percent were not taking their prescribed anti-hypertensive medication. 59 in non-cocaine users), more likely to be African American, and all smoked cigarettes. Cocaine users were younger (average age of 41 vs. Of the 38 cases found, 37 percent were related to cocaine use. They recorded demographic information as well as information on cocaine use and coronary risk factors. Researchers reviewed hospital charts from 1981-2001 looking for cases of aortic dissection. After 48 hours the death rate rises to about 50 percent.” For untreated aortic dissection, the mortality rate can be as high as 35 percent within the first 24 hours. “It’s very important to get a rapid diagnosis. “In urban settings, aortic dissection should be considered when young people come to the emergency room with severe chest pain, especially if they have other risk factors like high blood pressure and smoking,” says Hsue. The dissection may stop blood from reaching critical organs, or even cause the aorta to rupture. This may tear the lining of the vessel, which can allow blood to enter and rip it even further, says Hsue. Hsue, M.D., division of cardiology, San Francisco General Hospital.Ĭocaine use causes an increase in stress hormones that can cause blood pressure to quickly rise. “Most patients came to the hospital with chest pain shortly after drug use, and one developed symptoms while smoking crack,” says primary researcher Priscilla Y. However, researchers at San Francisco General Hospital noticed younger patients coming to the hospital with aortic dissection due to cocaine use. Cocaine use is not a commonly recognized risk factor for aortic dissection, which usually occurs in older people with high blood pressure. The condition called aortic dissection occurs when the lining of the aorta – the major blood vessel carrying blood from the heart – tears, exposing the inner layer.
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