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Title: | Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses | Authors: | Kapeli, K Pratt, G.A Vu, A.Q Hutt, K.R Martinez, F.J Sundararaman, B Batra, R Freese, P Lambert, N.J Huelga, S.C Chun, S.J Liang, T.Y Chang, J Donohue, J.P Shiue, L Zhang, J Zhu, H Cambi, F Kasarskis, E Hoon, S Ares, M Burge, C.B Ravits, J Rigo, F Yeo, G.W |
Keywords: | fused in sarcoma protein messenger RNA protein TAF15 RNA RNA binding protein TAR DNA binding protein unclassified drug antisense oligonucleotide DNA binding protein FUS protein, human FUS protein, mouse messenger RNA RNA binding protein FUS small interfering RNA TAF15 protein, human TAF15 protein, mouse TATA binding protein associated factor TDP-43 protein, human TDP-43 protein, mouse brain chemical binding genetic engineering genetic marker mutation nervous system disorder protein RNA rodent 3' untranslated region 5' untranslated region adult alternative RNA splicing amyotrophic lateral sclerosis animal cell animal tissue Article case report controlled study down regulation female gene expression gene expression regulation gene mutation genetic variability human intron motoneuron mouse neural stem cell nonhuman nucleotide motif nucleotide sequence protein RNA binding RNA metabolism RNA stability turnover time amyotrophic lateral sclerosis animal biology C57BL mouse disease model fibroblast gene knockdown genetics high throughput sequencing induced pluripotent stem cell metabolism mutation primary cell culture procedures sequence analysis 3' Untranslated Regions Alternative Splicing Amyotrophic Lateral Sclerosis Animals Computational Biology Disease Models, Animal DNA-Binding Proteins Female Fibroblasts Gene Knockdown Techniques High-Throughput Nucleotide Sequencing Humans Induced Pluripotent Stem Cells Introns Mice Mice, Inbred C57BL Motor Neurons Mutation Oligonucleotides, Antisense Primary Cell Culture RNA, Messenger RNA, Small Interfering RNA-Binding Protein FUS Sequence Analysis, RNA TATA-Binding Protein Associated Factors |
Issue Date: | 2016 | Publisher: | Nature Publishing Group | Citation: | Kapeli, K, Pratt, G.A, Vu, A.Q, Hutt, K.R, Martinez, F.J, Sundararaman, B, Batra, R, Freese, P, Lambert, N.J, Huelga, S.C, Chun, S.J, Liang, T.Y, Chang, J, Donohue, J.P, Shiue, L, Zhang, J, Zhu, H, Cambi, F, Kasarskis, E, Hoon, S, Ares, M, Burge, C.B, Ravits, J, Rigo, F, Yeo, G.W (2016). Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. Nature Communications 7 : 12143. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms12143 | Abstract: | The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ?4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3? untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism. | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/174950 | ISSN: | 20411723 | DOI: | 10.1038/ncomms12143 |
Appears in Collections: | Elements Staff Publications |
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