Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.
Katannya Kapeli, Gabriel A Pratt, Anthony Q Vu, Kasey R Hutt, Fernando J Martinez, Balaji Sundararaman, Ranjan Batra, Peter Freese, Nicole J Lambert, Stephanie C Huelga, Seung J Chun, Tiffany Y Liang, Jeremy Chang, John P Donohue, Lily Shiue, Jiayu Zhang, Haining Zhu, Franca Cambi, Edward Kasarskis, Shawn Hoon, Manuel Ares, Christopher B Burge, John Ravits, Frank Rigo, Gene W Yeo
Nature communications · 2016 · Vol. 7 · pp. 12143
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.
Linked datasets 6
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_Stability]
Homo sapiens
36 data files
| File | Type | Size |
|---|---|---|
| NPC0_ctrl.fastq.gz | RNA-Seq | 402.6 MB |
| NPC0_FUS.fastq.gz | RNA-Seq | 219.4 MB |
| NPC0_TAF15.fastq.gz | RNA-Seq | 66.1 MB |
| NPC15_ctrl.fastq.gz | RNA-Seq | 1.6 GB |
| NPC15_FUS.fastq.gz | RNA-Seq | 361.2 MB |
| NPC15_TAF15.fastq.gz | RNA-Seq | 157.1 MB |
| NPC1_ctrl.fastq.gz | RNA-Seq | 282.1 MB |
| NPC1_FUS.fastq.gz | RNA-Seq | 235.2 MB |
| NPC1_TAF15.fastq.gz | RNA-Seq | 1.3 GB |
| NPC2_ctrl.fastq.gz | RNA-Seq | 322.8 MB |
| NPC2_FUS.fastq.gz | RNA-Seq | 246.1 MB |
| NPC2_TAF15.fastq.gz | RNA-Seq | 485.3 MB |
| NPC30_ctrl.fastq.gz | RNA-Seq | 442.8 MB |
| NPC30_FUS.fastq.gz | RNA-Seq | 251.7 MB |
| NPC30_TAF15.fastq.gz | RNA-Seq | 181.5 MB |
| NPC4_ctrl.fastq.gz | RNA-Seq | 396.3 MB |
| NPC4_FUS.fastq.gz | RNA-Seq | 413.6 MB |
| NPC4_TAF15.fastq.gz | RNA-Seq | 233.8 MB |
| SRR3153311_GSM2056814 | RNA-Seq | 402.0 MB |
| SRR3153312_GSM2056815 | RNA-Seq | 219.0 MB |
| SRR3153313_GSM2056816 | RNA-Seq | 66.0 MB |
| SRR3153314_GSM2056817 | RNA-Seq | 1.6 GB |
| SRR3153315_GSM2056818 | RNA-Seq | 361.0 MB |
| SRR3153316_GSM2056819 | RNA-Seq | 157.0 MB |
| SRR3153317_GSM2056820 | RNA-Seq | 282.0 MB |
| SRR3153318_GSM2056821 | RNA-Seq | 235.0 MB |
| SRR3153319_GSM2056822 | RNA-Seq | 1.3 GB |
| SRR3153320_GSM2056823 | RNA-Seq | 322.0 MB |
| SRR3153321_GSM2056824 | RNA-Seq | 246.0 MB |
| SRR3153322_GSM2056825 | RNA-Seq | 485.0 MB |
| SRR3153323_GSM2056826 | RNA-Seq | 442.0 MB |
| SRR3153324_GSM2056827 | RNA-Seq | 251.0 MB |
| SRR3153325_GSM2056828 | RNA-Seq | 181.0 MB |
| SRR3153326_GSM2056829 | RNA-Seq | 396.0 MB |
| SRR3153327_GSM2056830 | RNA-Seq | 413.0 MB |
| SRR3153328_GSM2056831 | RNA-Seq | 233.0 MB |
Distinct and shared molecular targets and functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [CLIP-Seq]
Mus musculus
4 data files
| File | Type | Size |
|---|---|---|
| SRR3153187_GSM2056777 | RIP-Seq | 6.0 GB |
| SRR3153188_GSM2056777 | RIP-Seq | 3.8 GB |
| TAF15_1.fastq.gz | RIP-Seq | 6.0 GB |
| TAF15_2.fastq.gz | RIP-Seq | 3.8 GB |
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_mouse]
Mus musculus
8 data files
| File | Type | Size |
|---|---|---|
| KK1.fastq.gz | RNA-Seq | 942.2 MB |
| KK2.fastq.gz | RNA-Seq | 1.1 GB |
| KK7.fastq.gz | RNA-Seq | 1.1 GB |
| KK8.fastq.gz | RNA-Seq | 1.1 GB |
| SRR3153279_GSM2056810 | RNA-Seq | 1.1 GB |
| SRR3153280_GSM2056811 | RNA-Seq | 1.1 GB |
| SRR3153281_GSM2056812 | RNA-Seq | 942.0 MB |
| SRR3153282_GSM2056813 | RNA-Seq | 1.1 GB |
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_human]
Homo sapiens
32 data files
| File | Type | Size |
|---|---|---|
| AV_GY6_2_1_CTGAAGC_L001_R1.fastq.gz | RNA-Seq | 395.5 MB |
| AV_GY7_3_1_CGGCTAT_L001_R1.fastq.gz | RNA-Seq | 697.7 MB |
| AV_GY7_6_1_TCCGGAG_L005_R1.fastq.gz | RNA-Seq | 1011.3 MB |
| AV_KIN1ALS17_3_1_TAATGCG_L002_R1.fastq.gz | RNA-Seq | 737.8 MB |
| AV_KIN1ALS6_4_1_TCCGCGA_L003_R1.fastq.gz | RNA-Seq | 1.0 GB |
| AV_KIN1ALS6_4_shSCR_1_CTGAAGC_L004_R1.fastq.gz | RNA-Seq | 455.0 MB |
| FUS_shRNA_1.fastq.gz | RNA-Seq | 3.2 GB |
| FUS_shRNA_2.fastq.gz | RNA-Seq | 3.1 GB |
| FUS_TAF15_shRNA_1.fastq.gz | RNA-Seq | 3.2 GB |
| FUS_TAF15_shRNA_2.fastq.gz | RNA-Seq | 2.8 GB |
| Scrm_1.fastq.gz | RNA-Seq | 1.5 GB |
| Scrm_2.fastq.gz | RNA-Seq | 2.2 GB |
| SRR3153251_GSM2056794 | RNA-Seq | 3.2 GB |
| SRR3153252_GSM2056795 | RNA-Seq | 3.1 GB |
| SRR3153253_GSM2056796 | RNA-Seq | 3.2 GB |
| SRR3153254_GSM2056797 | RNA-Seq | 2.8 GB |
| SRR3153255_GSM2056798 | RNA-Seq | 1.5 GB |
| SRR3153256_GSM2056799 | RNA-Seq | 2.2 GB |
| SRR3153257_GSM2056800 | RNA-Seq | 3.1 GB |
| SRR3153258_GSM2056801 | RNA-Seq | 2.6 GB |
| SRR3153259_GSM2056802 | RNA-Seq | 2.9 GB |
| SRR3153260_GSM2056803 | RNA-Seq | 1.9 GB |
| SRR3153261_GSM2056804 | RNA-Seq | 395.0 MB |
| SRR3153262_GSM2056805 | RNA-Seq | 697.0 MB |
| SRR3153263_GSM2056806 | RNA-Seq | 1011.0 MB |
| SRR3153264_GSM2056807 | RNA-Seq | 737.0 MB |
| SRR3153265_GSM2056808 | RNA-Seq | 1.0 GB |
| SRR3153266_GSM2056809 | RNA-Seq | 455.0 MB |
| TAF15_shRNA_1.fastq.gz | RNA-Seq | 3.1 GB |
| TAF15_shRNA_2.fastq.gz | RNA-Seq | 2.6 GB |
| TDP43_shRNA_1.fastq.gz | RNA-Seq | 2.9 GB |
| TDP43_shRNA_2.fastq.gz | RNA-Seq | 1.9 GB |
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [array]
Mus musculus
Potentially related datasets 3
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
| Accession | Source | Title |
|---|---|---|
| ENCSR827QYL | ENCSR · ENCODE | RNA Bind-n-Seq (RBNS) pulldown experiment against TAF15 |
| ENCSR936LOF | ENCSR · ENCODE | RNA Bind-n-Seq (RBNS) pulldown experiment against FUS |
| GSE77707 | GSE · GEO GEO ↗ | Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses |
Analysis pipelines 6
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE77699 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 2 | GSE77699 |
| GSE77700 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 3 | GSE77700 |
| GSE77702 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 5 | GSE77702 |
| GSE77703 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 5 | GSE77703 |
| GSE77704 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 5 | GSE77704 |
| GSE77707 Microarray Data Processing geo_data_processing | Microarray | 2 | GSE77707 |
Funding 7 grants
| Grant | Funder |
|---|---|
| R01 HG004659 | NHGRI NIH HHS (United States) |
| T32 GM008666 | NIGMS NIH HHS (United States) |
| T32 GM087237 | NIGMS NIH HHS (United States) |
| U54 HG007005 | NHGRI NIH HHS (United States) |
| R01 NS075449 | NINDS NIH HHS (United States) |
| R01 NS077284 | NINDS NIH HHS (United States) |
| I01 BX002149 | BLRD VA (United States) |