PMID- 25980610 OWN - NLM STAT- MEDLINE DCOM- 20150930 LR - 20151119 IS - 1873-3468 (Electronic) IS - 0014-5793 (Linking) VI - 589 IP - 15 DP - 2015 Jul 8 TI - Lymphotoxin alpha, a novel target of posttranscriptional gene regulation by HuR in HepG2 cells. PG - 1943-50 LID - S0014-5793(15)00391-9 [pii] LID - 10.1016/j.febslet.2015.05.015 [doi] AB - The role of the RNA-binding protein human antigen R (HuR) in hepatocarcinogenesis is still elusive. By employing short hairpin (sh)RNA-dependent knockdown approach, we demonstrate that lymphotoxin alpha (LTalpha) is a target of posttranscriptional gene regulation by HuR in hepatocellular carcinoma (HepG2) cells. Consequently, the increased mRNA decay upon HuR depletion significantly affects lymphotoxin expression at both, the mRNA and protein level. Biotin-pulldown assay showed that HuR specifically interacts with the 3'-untranslated region (3'-UTR) of the LTalpha mRNA. Furthermore, electrophoretic mobility shift assay (EMSA) implicates that the RNA-binding critically depends on the RNA recognition motif 2 (RRM2) and the hinge region of HuR. CI - Copyright (c) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. FAU - Steinmeyer, Nico AU - Steinmeyer N AD - pharmazentrum frankfurt/ZAFES, Klinikum der Goethe-Universitat Frankfurt, Frankfurt am Main, Germany. FAU - Doller, Anke AU - Doller A AD - Industrielle Biotechnologie, Fakultat Ingenieurwissenschaften, Hochschule Ansbach, Germany. FAU - Biyanee, Abhiruchi AU - Biyanee A AD - pharmazentrum frankfurt/ZAFES, Klinikum der Goethe-Universitat Frankfurt, Frankfurt am Main, Germany. FAU - Brauss, Thilo AU - Brauss T AD - Institut fur Biochemie I (Pathobiochemie), Klinikum der Goethe-Universitat Frankfurt, Frankfurt am Main, Germany. FAU - Schmid, Tobias AU - Schmid T AD - Institut fur Biochemie I (Pathobiochemie), Klinikum der Goethe-Universitat Frankfurt, Frankfurt am Main, Germany. FAU - Pfeilschifter, Josef AU - Pfeilschifter J AD - pharmazentrum frankfurt/ZAFES, Klinikum der Goethe-Universitat Frankfurt, Frankfurt am Main, Germany. FAU - Eberhardt, Wolfgang AU - Eberhardt W AD - pharmazentrum frankfurt/ZAFES, Klinikum der Goethe-Universitat Frankfurt, Frankfurt am Main, Germany. Electronic address: w.eberhardt@em.uni-frankfurt.de. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150514 PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (3' Untranslated Regions) RN - 0 (ELAV Proteins) RN - 0 (Lymphotoxin-alpha) RN - 0 (RNA, Messenger) SB - IM MH - 3' Untranslated Regions MH - ELAV Proteins/genetics/*physiology MH - Electrophoretic Mobility Shift Assay MH - *Gene Expression Regulation MH - Gene Knockdown Techniques MH - Hep G2 Cells MH - Humans MH - Lymphotoxin-alpha/*genetics/metabolism MH - *RNA Processing, Post-Transcriptional MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction OTO - NOTNLM OT - AU-rich element OT - Hepatocellular carcinoma OT - Lymphotoxin alpha OT - mRNA-stability EDAT- 2015/05/20 06:00 MHDA- 2015/10/01 06:00 CRDT- 2015/05/19 06:00 PHST- 2015/03/03 00:00 [received] PHST- 2015/04/24 00:00 [revised] PHST- 2015/05/06 00:00 [accepted] PHST- 2015/05/19 06:00 [entrez] PHST- 2015/05/20 06:00 [pubmed] PHST- 2015/10/01 06:00 [medline] AID - S0014-5793(15)00391-9 [pii] AID - 10.1016/j.febslet.2015.05.015 [doi] PST - ppublish SO - FEBS Lett. 2015 Jul 8;589(15):1943-50. doi: 10.1016/j.febslet.2015.05.015. Epub 2015 May 14.