Abstract
U1 small ribonucleoproteins demonstrate proteopathy in Alzheimer's disease, and their inhibition modulates the expression of the amyloid precursor protein (APP). We sought to determine whether this effect on the APP expression is a universal result of different kinds of RNA splicing inhibitions. We treated cells with two chemical RNA splicing inhibitors: isoginkgetin (IGK) and spliceostatin A (SSA), in which SSA reduced the APP expression, whereas IGK substantially increased it. The following western blot and reverse transcription polymerase chain reaction analyses showed that the APP expression under the IGK treatment has distinct protein forms, but the total mRNA level was nearly unchanged despite a slight switch within its three major transcripts. Further analysis revealed that the APP-increasing effect of IGK depended on protein translation and might involve inhibition in the degradation system. By immunocytochemistry, the APP likely redistributed from Golgi to endoplasmic reticulum (ER) in cells treated with IGK. When compared to the well-characterized ER-to-Golgi transport inhibitor brefeldin A, IGK showed similar APP expression patterns on the western blot. In summary, we not only determined the diverse effects of RNA sp...Continue Reading
References
Nov 26, 1992·Nature·J G DonaldsonR D Klausner
Nov 1, 1991·Cell·H R Pelham
Mar 10, 1989·Cell·J Lippincott-SchwartzR D Klausner
Dec 1, 1995·The Journal of Cell Biology·N NakamuraG Warren
Apr 16, 1998·The Journal of Biological Chemistry·S TomitaT Suzuki
Aug 1, 2006·Lancet·Kaj BlennowHenrik Zetterberg
Nov 24, 2006·Molecular Cancer Therapeutics·Sang-Oh YoonAn-Sik Chung
Jul 24, 2007·Nature Chemical Biology·Daisuke KaidaMinoru Yoshida
Sep 1, 2007·The Journal of Endocrinology·Guohong LiuQi-Xiang Li
Oct 2, 2008·The Journal of Biological Chemistry·Kristine O'BrienMelissa J Moore
Oct 22, 2010·The Journal of Biological Chemistry·Nikolai D BelyaevAnthony J Turner
Dec 7, 2011·The Journal of Biological Chemistry·Qinxi GuoHui Zheng
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Christian HaassSangram Sisodia
Jun 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Regina Wai-Yan ChoyRandy Schekman
Nov 6, 2012·Nature Reviews. Drug Discovery·Sophie BonnalJuan Valcárcel
Dec 25, 2012·Nature Cell Biology·Amber R English, Gia K Voeltz
Jul 23, 2013·Cell·Dennis J Selkoe
Sep 12, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bing BaiJunmin Peng
Nov 12, 2013·Cell·Rita GuerreiroJohn Hardy
Feb 28, 2014·Brain Pathology·Chadwick M HalesJames J Lah
Apr 30, 2014·Molecular Neurodegeneration·Chadwick M HalesJames J Lah