TY - JOUR AB - Recent years have seen a rise in publications demonstrating coupling between transcription and mRNA decay. This coupling most often accompanies cellular processes that involve transitions in gene expression patterns, for example during mitotic division and cellular differentiation and in response to cellular stress. Transcription can affect the mRNA fate by multiple mechanisms. The most novel finding is the process of co-transcriptional imprinting of mRNAs with proteins, which in turn regulate cytoplasmic mRNA stability. Transcription therefore is not only a catalyst of mRNA synthesis but also provides a platform that enables imprinting, which coordinates between transcription and mRNA decay. Here we present an overview of the literature, which provides the evidence of coupling between transcription and decay, review the mechanisms and regulators by which the two processes are coupled, discuss why such coupling is beneficial and present a new model for regulation of gene expression. This article is part of a Special Issue entitled: RNA Decay mechanisms. AD - Albert Einstein College of Medicine, Bronx, NY 10461, USA. AN - 23337853 AU - Haimovich, G. AU - Choder, M. AU - Singer, R. H. AU - Trcek, T. C1 - 7 C2 - PMC3891481 CN - 11111 DA - Jun-Jul DO - 10.1016/j.bbagrm.2013.01.004 S1874-9399(13)00008-4 [pii] DP - Nlm ET - 2013/01/23 KW - Cytoplasm/genetics Gene Expression Regulation, Fungal Genomic Imprinting Humans Poly(A)-Binding Proteins/genetics RNA Polymerase II/genetics RNA Stability/*genetics RNA, Messenger/*genetics Ribonucleases/genetics Saccharomyces cerevisiae/*genetics Saccharomyces cerevisiae Proteins/genetics *Transcription, Genetic L1 - internal-pdf://1823670337/Haimovich-2013-The fate of the messenger is pr.pdf LA - eng LB - 23337853 M1 - 6-7 N1 - Haimovich, Gal Choder, Mordechai Singer, Robert H Trcek, Tatjana /GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Netherlands Biochimica et biophysica acta Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):643-53. doi: 10.1016/j.bbagrm.2013.01.004. Epub 2013 Jan 19. PY - 2013 RI - 2013 from pubmed SN - 0006-3002 (Print) 0006-3002 (Linking) SP - 643-53 ST - The fate of the messenger is pre-determined: a new model for regulation of gene expression T2 - Biochim Biophys Acta TI - The fate of the messenger is pre-determined: a new model for regulation of gene expression TT - GM57071, R01 GM057071 UR - http://www.ncbi.nlm.nih.gov/pubmed/23337853 http://ac.els-cdn.com/S1874939913000084/1-s2.0-S1874939913000084-main.pdf?_tid=7f315780-c036-11e3-a49c-00000aacb35e&acdnat=1397082784_422e68d44bc3d6c315f10c6b2d1630d4 VL - 1829 ID - 1 ER - TY - JOUR AB - Adopted orphan nuclear receptor (NR), pregnane X receptor (PXR), plays a central role in the regulation of xeno- and endobiotic metabolism. Since the discovery of the functional role of PXR in 1998, there is evolving evidence for the role of PXR agonists in abrogating metabolic pathophysiology (e.g., cholestasis, hypercholesterolemia, and inflammation). However, more recently, it is clear that PXR is also an important mediator of adverse xeno- (e.g., enhances acetaminophen toxicity) and endobiotic (e.g., hepatic steatosis) metabolic phenotypes. Moreover, in cancer therapeutics, PXR activation can induce drug resistance, and there is growing evidence for tissue-specific enhancement of the malignant phenotype. Thus, in these instances, there may be a role for PXR antagonists. However, as opposed to the discovery efforts for PXR agonists, there are only a few antagonists described. The mode of action of these antagonists (e.g., sulforaphane) remains less clear. Our laboratory efforts have focused on this question. Since the original discovery of azoles analogs as PXR antagonists, we have preliminarily defined an important PXR antagonist pharmacophore and developed less-toxic PXR antagonists. In this review, we describe our published and unpublished findings on recent structure-function studies involving the azole chemical scaffold. Further work in the future is needed to fully define potent, more-selective PXR antagonists that may be useful in clinical application. AD - Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. sridhar.mani@einstein.yu.edu AN - 23330542 AU - Mani, S. AU - Dou, W. AU - Redinbo, M. R. C1 - 7 C2 - PMC3583015 CN - 11114 DA - Feb DO - 10.3109/03602532.2012.746363 DP - Nlm ET - 2013/01/22 KW - Animals Azoles/pharmacokinetics/pharmacology Humans Metabolic Detoxication, Drug Receptors, Steroid/*antagonists & inhibitors/*metabolism Xenobiotics/pharmacokinetics/pharmacology L1 - internal-pdf://3452567633/Mani-2013-PXR antagonists and implication in d.pdf LA - eng LB - 23330542 M1 - 1 N1 - Mani, Sridhar Dou, Wei Redinbo, Matthew R Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review England Drug metabolism reviews Drug Metab Rev. 2013 Feb;45(1):60-72. doi: 10.3109/03602532.2012.746363. PY - 2013 RI - 2013 from pubmed SN - 1097-9883 (Electronic) 0360-2532 (Linking) SP - 60-72 ST - PXR antagonists and implication in drug metabolism T2 - Drug Metab Rev TI - PXR antagonists and implication in drug metabolism TT - CA 127231,R01 CA127231 UR - http://www.ncbi.nlm.nih.gov/pubmed/23330542 http://informahealthcare.com/doi/pdfplus/10.3109/03602532.2012.746363 VL - 45 ID - 3 ER - TY - JOUR AB - BACKGROUND: Most drug treatment patients smoke cigarettes, yet few data exist on the prevalence and outcomes of varenicline treatment among smokers with comorbid substance use and psychiatric disorders. METHODS: We reviewed all patient charts of opioid-dependent smokers prescribed varenicline between May 2006 and December 2009 in two urban methadone clinics that also provide on-site medical and psychiatric care. We assessed prevalence, adverse events, and effectiveness of varenicline treatment in this cohort. RESULTS: We identified 575 smokers among 690 patients (83.3%), and assessed 82 courses of varenicline treatment prescribed to 70 smokers. Both cardiovascular risk factors and psychiatric illness were highly prevalent among those prescribed varenicline: hypertension, 51%; hyperlipidemia, 23%; diabetes, 20%; depression, 53%; anxiety, 30%; psychotic disorders, 10%; bipolar disorder, 8.6%. Of 82 varenicline courses, nine (11%) were discontinued due to adverse events and two due to depressive symptoms. One patient initiated new psychiatric medications within six months of initiating varenicline, but did not discontinue varenicline. There were no reports of suicidal ideation, agitation prompting clinical intervention, or psychiatric hospitalization. There were no incident cardiac or vascular events within six months of varenicline prescription. Some (8.6%) varenicline-treated smokers quit smoking, and cessation was significantly associated with varenicline treatment duration. CONCLUSIONS: Despite substantial comorbidity, opioid-dependent smokers receiving integrated substance abuse, medical and psychiatric care had few documented adverse events with varenicline treatment. Methadone patients will likely experience little harm and a great deal of benefit from treatment with varenicline for smoking cessation. AD - Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10467, USA. snahvi@dosa.aecom.yu.edu AN - 23332438 AU - Nahvi, S. AU - Wu, B. AU - Richter, K. P. AU - Bernstein, S. L. AU - Arnsten, J. H. C1 - 6 C2 - PMC3762456 CN - 11113 DA - Sep 1 DO - 10.1016/j.drugalcdep.2012.12.026 S0376-8716(12)00502-9 [pii] DP - Nlm ET - 2013/01/22 L1 - internal-pdf://2272264257/Nahvi-2013-Low incidence of adverse events fol.pdf LA - eng LB - 23332438 M1 - 1-2 N1 - Nahvi, Shadi Wu, Bryan Richter, Kimber P Bernstein, Steven L Arnsten, Julia H Research Support, N.I.H., Extramural Ireland Drug and alcohol dependence Drug Alcohol Depend. 2013 Sep 1;132(1-2):47-52. doi: 10.1016/j.drugalcdep.2012.12.026. Epub 2013 Jan 17. PY - 2013 RI - 2013 from pubmed SN - 1879-0046 (Electronic) 0376-8716 (Linking) SP - 47-52 ST - Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness T2 - Drug Alcohol Depend TI - Low incidence of adverse events following varenicline initiation among opioid dependent smokers with comorbid psychiatric illness TT - K23 DA025736,R25 DA023021,UL1 RR025750 UR - http://www.ncbi.nlm.nih.gov/pubmed/23332438 http://ac.els-cdn.com/S0376871612005029/1-s2.0-S0376871612005029-main.pdf?_tid=d9415950-c036-11e3-b516-00000aab0f6c&acdnat=1397082935_3ddd7d71209fd6cd5a4bf571f581f7a4 VL - 132 ID - 2 ER - TY - JOUR AD - Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. richard.kitsis@einstein.yu.edu. AN - 23371896 AU - Whelan, R. S. AU - Konstantinidis, K. AU - Xiao, R. P. AU - Kitsis, R. N. C1 - 2 C2 - PMC3883759 CN - 11119 DA - Feb 1 DO - 10.1161/CIRCRESAHA.113.300805 112/3/408 [pii] DP - Nlm ET - 2013/02/02 KW - Animals Cyclic AMP-Dependent Protein Kinases/*metabolism Heart Failure/*enzymology/*prevention & control Intracellular Signaling Peptides and Proteins/*metabolism Myocytes, Cardiac/*enzymology Receptors, Adrenergic, beta/*metabolism L1 - internal-pdf://1123090529/Whelan-2013-Cardiomyocyte life-death decisions.pdf LA - eng LB - 23371896 M1 - 3 N1 - Whelan, Russell S Konstantinidis, Klitos Xiao, Rui-Ping Kitsis, Richard N Comment Editorial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Circulation research Circ Res. 2013 Feb 1;112(3):408-10. doi: 10.1161/CIRCRESAHA.113.300805. PY - 2013 RI - 2013 from pubmed SN - 1524-4571 (Electronic) 0009-7330 (Linking) SP - 408-10 ST - Cardiomyocyte life-death decisions in response to chronic beta-adrenergic signaling T2 - Circ Res TI - Cardiomyocyte life-death decisions in response to chronic beta-adrenergic signaling TT - 1R03DA031671-02,5R01HL060665-14,5U01HL099776-04 UR - http://www.ncbi.nlm.nih.gov/pubmed/23371896 http://circres.ahajournals.org/content/112/3/408.full.pdf VL - 112 ID - 4 ER -