Suppression of 5' splice-sites through multiple exonic motifs by hnRNP L

作者: Tiing Jen Loh , Namjeong Choi , Heegyum Moon , Ha Na Jang , Yongchao Liu

DOI: 10.1016/J.BBAGRM.2017.01.010

关键词: ExonBiologyHeterogeneous-Nuclear Ribonucleoprotein LAlternative splicingKLF6spliceGeneticsRNA splicingRegulation of gene expressionExonic splicing enhancer

摘要: Selection of 5' splice-sites (5'SS) in alternative splicing plays an important role gene regulation. Although regulatory mechanisms heterogeneous nuclear ribonucleoprotein L (hnRNP L), a well-known protein, have been studied substantial level, its 5'SS selection is not thoroughly defined. By using KLF6 pre-mRNA model, we demonstrate this report that hnRNP inhibits proximal but promotes two consecutive distal splicing, antagonizing SRSF1 roles splicing. In addition, three CA-rich sequences CA cassette immediately upstream the are all required for functions. Importantly, CA-cassette locations on exon do affect roles. We further show 5'SSs essential activities. Notably, Bcl-x model contains includes elements at exon, also suppresses nearby activation. Taken together, conclude through multiple exonic motifs.

参考文章(70)
Yu Fu, Binlu Huang, Zhen Shi, Jiayu Han, Ying Wang, Jieqiong Huangfu, Wei Wu, SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing β-catenin biosynthesis. Embo Molecular Medicine. ,vol. 5, pp. 737- 750 ,(2013) , 10.1002/EMMM.201202218
Tiing Jen Loh, Sunghee Cho, Heegyum Moon, Ha Na Jang, Darren Reece Williams, Da-Woon Jung, Il-Chul Kim, Claudia Ghigna, Giuseppe Biamonti, Xuexiu Zheng, Haihong Shen, hnRNP L inhibits CD44 V10 exon splicing through interacting with its upstream intron. Biochimica et Biophysica Acta. ,vol. 1849, pp. 743- 750 ,(2015) , 10.1016/J.BBAGRM.2015.01.004
Analisa DiFeo, John A. Martignetti, Goutham Narla, The role of KLF6 and its splice variants in cancer therapy. Drug Resistance Updates. ,vol. 12, pp. 1- 7 ,(2009) , 10.1016/J.DRUP.2008.11.001
Nobuyuki Matsumoto, Atsushi Kubo, Huixian Liu, Kuniharu Akita, Friedrich Laub, Francesco Ramirez, Gordon Keller, Scott L. Friedman, Developmental regulation of yolk sac hematopoiesis by Kruppel-like factor 6. Blood. ,vol. 107, pp. 1357- 1365 ,(2006) , 10.1182/BLOOD-2005-05-1916
Jingyi Hui, Karl Stangl, William S. Lane, Albrecht Bindereif, HnRNP L stimulates splicing of the eNOS gene by binding to variable-length CA repeats Nature Structural & Molecular Biology. ,vol. 10, pp. 33- 37 ,(2003) , 10.1038/NSB875
Goutham Narla, Analisa DiFeo, Yolanda Fernandez, Saravana Dhanasekaran, Fei Huang, Jaya Sangodkar, Eldad Hod, Devin Leake, Scott L. Friedman, Simon J. Hall, Arul M. Chinnaiyan, William L. Gerald, Mark A. Rubin, John A. Martignetti, KLF6-SV1 overexpression accelerates human and mouse prostate cancer progression and metastasis Journal of Clinical Investigation. ,vol. 118, pp. 2711- 2721 ,(2008) , 10.1172/JCI34780
Sigal Kremer-Tal, Helen L. Reeves, Goutham Narla, Swan N. Thung, Myron Schwartz, Analisa Difeo, Amanda Katz, Jordi Bruix, Paulette Bioulac-Sage, John A. Martignetti, Scott L. Friedman, Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma. Hepatology. ,vol. 40, pp. 1047- 1052 ,(2004) , 10.1002/HEP.20460
Olga Anczuków, Avi Z Rosenberg, Martin Akerman, Shipra Das, Lixing Zhan, Rotem Karni, Senthil K Muthuswamy, Adrian R Krainer, The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation Nature Structural & Molecular Biology. ,vol. 19, pp. 220- 228 ,(2012) , 10.1038/NSMB.2207
Guodong Liu, Aleh Razanau, Yan Hai, Jiankun Yu, Muhammad Sohail, Vincent G. Lobo, Jiayou Chu, Sam K. P. Kung, Jiuyong Xie, A Conserved Serine of Heterogeneous Nuclear Ribonucleoprotein L (hnRNP L) Mediates Depolarization-regulated Alternative Splicing of Potassium Channels Journal of Biological Chemistry. ,vol. 287, pp. 22709- 22716 ,(2012) , 10.1074/JBC.M112.357343