TDP-43 regulates site-specific 2′-O-methylation of U1 and U2 snRNAs via controlling the Cajal body localization of a subset of C/D scaRNAs

作者: Keiichi Izumikawa , Yuko Nobe , Hideaki Ishikawa , Yoshio Yamauchi , Masato Taoka

DOI: 10.1093/NAR/GKZ086

关键词: Cajal bodyRibonucleoproteinNucleolusCell biologyRNASmall nuclear RNAPopulationBiologyRNA splicingsnRNP

摘要: TDP-43 regulates cellular levels of Cajal bodies (CBs) that provide platforms for the assembly and RNA modifications small nuclear ribonucleoproteins (snRNPs) involved in pre-mRNA splicing. Alterations these snRNPs may be linked to pathogenesis amyotrophic lateral sclerosis. However, specific roles CBs remain unknown. Here, we demonstrate CB localization four UG-rich motif-bearing C/D-box-containing body-specific RNAs (C/D scaRNAs; i.e. scaRNA2, 7, 9 28) through direct binding scaRNAs. enhances a CB-localizing protein, WD40-repeat protein 79 (WDR79), subpopulation scaRNA2 scaRNA28; remaining population C/D scaRNAs was localized CB-like structures even with WDR79 depletion. Depletion TDP-43, contrast, shifted scaRNAs, mainly into nucleolus, as well destabilizing reduced site-specific 2'-O-methylation U1 U2 snRNAs, including at 70A snRNA and, 19G, 25G, 47U 61C snRNA. Collectively, suggest have separate determining subsets H/ACA

参考文章(84)
James Tollervey, Jernej Ule, Marco Baralle, Emanuele Buratti, Francisco E Baralle, Youhna M Ayala, Laura De Conti, S Eréndira Avendaño-Vázquez, Ashish Dhir, Maurizio Romano, Andrea D'Ambrogio, TDP-43 regulates its mRNA levels through a negative feedback loop The EMBO Journal. ,vol. 30, pp. 277- 288 ,(2011) , 10.1038/EMBOJ.2010.310
J. Sreedharan, I. P. Blair, V. B. Tripathi, X. Hu, C. Vance, B. Rogelj, S. Ackerley, J. C. Durnall, K. L. Williams, E. Buratti, F. Baralle, J. de Belleroche, J. D. Mitchell, P. N. Leigh, A. Al-Chalabi, C. C. Miller, G. Nicholson, C. E. Shaw, TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis Science. ,vol. 319, pp. 1668- 1672 ,(2008) , 10.1126/SCIENCE.1154584
Hitomi Tsuiji, Yohei Iguchi, Asako Furuya, Ayane Kataoka, Hiroyuki Hatsuta, Naoki Atsuta, Fumiaki Tanaka, Yoshio Hashizume, Hiroyasu Akatsu, Shigeo Murayama, Gen Sobue, Koji Yamanaka, Spliceosome integrity is defective in the motor neuron diseases ALS and SMA Embo Molecular Medicine. ,vol. 5, pp. 221- 234 ,(2013) , 10.1002/EMMM.201202303
J. P. Ling, O. Pletnikova, J. C. Troncoso, P. C. Wong, TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD Science. ,vol. 349, pp. 650- 655 ,(2015) , 10.1126/SCIENCE.AAB0983
Chantelle F. Sephton, Can Cenik, Alper Kucukural, Eric B. Dammer, Basar Cenik, YuHong Han, Colleen M. Dewey, Frederick P. Roth, Joachim Herz, Junmin Peng, Melissa J. Moore, Gang Yu, Identification of neuronal RNA targets of TDP-43-containing Ribonucleoprotein complexes Journal of Biological Chemistry. ,vol. 286, pp. 1204- 1215 ,(2011) , 10.1074/JBC.M110.190884
Emanuele Buratti, Thilo Dörk, Elisabetta Zuccato, Franco Pagani, Maurizio Romano, Francisco E Baralle, Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping The EMBO Journal. ,vol. 20, pp. 1774- 1784 ,(2001) , 10.1093/EMBOJ/20.7.1774
Patricia Richard, Xavier Darzacq, Edouard Bertrand, Beáta E Jády, Céline Verheggen, Tamás Kiss, A common sequence motif determines the Cajal body‐specific localization of box H/ACA scaRNAs The EMBO Journal. ,vol. 22, pp. 4283- 4293 ,(2003) , 10.1093/EMBOJ/CDG394
Hiroshi Nakayama, Yoshio Yamauchi, Masato Taoka, Toshiaki Isobe, Direct Identification of Human Cellular MicroRNAs by Nanoflow Liquid Chromatography–High-Resolution Tandem Mass Spectrometry and Database Searching Analytical Chemistry. ,vol. 87, pp. 2884- 2891 ,(2015) , 10.1021/AC504378S
Shangxi Xiao, Teresa Sanelli, Samar Dib, David Sheps, Joseph Findlater, Juan Bilbao, Julia Keith, Lorne Zinman, Ekaterina Rogaeva, Janice Robertson, RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS Molecular and Cellular Neuroscience. ,vol. 47, pp. 167- 180 ,(2011) , 10.1016/J.MCN.2011.02.013