Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels.
Molecular cell
· 2018
· Vol. 69
(6)
· pp. 1005-1016.e7
Abstract
RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced UV crosslinking followed by immunoprecipitation (eCLIP) datasets for 126 RBPs to discover miR-encoding genomic loci that are statistically enriched for RBP binding. We find that 92% of RBPs interact directly with at least one miR locus, and that some interactions are cell line specific despite expression of the miR locus in both cell lines evaluated. We validated that ILF3 and BUD13 directly interact with and stabilize miR-144 and that BUD13 suppresses mir-210 processing to the mature species. We also observed that DDX3X regulates primary miR-20a, while LARP4 stabilizes precursor mir-210. Our approach to identifying regulators of miR loci can be applied to any user-defined RNA annotation, thereby guiding the discovery of uncharacterized regulators of RNA processing.
Publication Types
["Journal Article", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't"]
MeSH Terms
["Binding Sites", "Computational Biology", "Data Mining", "Databases, Genetic", "HEK293 Cells", "Hep G2 Cells", "Humans", "K562 Cells", "MicroRNAs", "Protein Binding", "RNA Interference", "RNA Precursors", "RNA Processing, Post-Transcriptional", "RNA Stability", "RNA-Binding Proteins"]
Funding
R01 HG004659
NHGRI NIH HHS
(United States)
T32 CA067754
NCI NIH HHS
(United States)
U54 HG007005
NHGRI NIH HHS
(United States)
Linked Datasets (1)
Systematic discovery of RNA binding proteins that control microRNA processing
Homo sapiens136 data files
| File | Type | Size |
|---|---|---|
| b8p42_hepg2_sh_bud13_r1_S24_L005_R1_001.fastq.gz | miRNA-Seq | 113.5 MB |
| b8p42_hepg2_sh_bud13_r1_S24_L005_R1_001.fastq.gz | miRNA-Seq | 113.5 MB |
| b8p42_hepg2_sh_bud13_r2_S36_L005_R1_001.fastq.gz | miRNA-Seq | 133.7 MB |
| b8p42_hepg2_sh_bud13_r2_S36_L005_R1_001.fastq.gz | miRNA-Seq | 133.7 MB |
| b8p42_hepg2_sh_control1_r1_S11_L005_R1_001.fastq.gz | miRNA-Seq | 120.4 MB |
| b8p42_hepg2_sh_control1_r1_S11_L005_R1_001.fastq.gz | miRNA-Seq | 120.4 MB |
| b8p42_hepg2_sh_control1_r2_S26_L005_R1_001.fastq.gz | miRNA-Seq | 179.8 MB |
| b8p42_hepg2_sh_control1_r2_S26_L005_R1_001.fastq.gz | miRNA-Seq | 179.8 MB |
| b8p42_hepg2_sh_control2_r1_S33_L005_R1_001.fastq.gz | miRNA-Seq | 118.2 MB |
| b8p42_hepg2_sh_control2_r1_S33_L005_R1_001.fastq.gz | miRNA-Seq | 118.2 MB |
| b8p42_hepg2_sh_control2_r2_S19_L005_R1_001.fastq.gz | miRNA-Seq | 108.7 MB |
| b8p42_hepg2_sh_control2_r2_S19_L005_R1_001.fastq.gz | miRNA-Seq | 108.7 MB |
| b8p42_hepg2_sh_ddx3x_r1_S15_L005_R1_001.fastq.gz | miRNA-Seq | 135.4 MB |
| b8p42_hepg2_sh_ddx3x_r1_S15_L005_R1_001.fastq.gz | miRNA-Seq | 135.4 MB |
| b8p42_hepg2_sh_ddx3x_r2_S29_L005_R1_001.fastq.gz | miRNA-Seq | 131.6 MB |
| b8p42_hepg2_sh_ddx3x_r2_S29_L005_R1_001.fastq.gz | miRNA-Seq | 131.6 MB |
| b8p42_hepg2_sh_dkc1_r1_S9_L005_R1_001.fastq.gz | miRNA-Seq | 167.7 MB |
| b8p42_hepg2_sh_dkc1_r1_S9_L005_R1_001.fastq.gz | miRNA-Seq | 167.7 MB |
| b8p42_hepg2_sh_dkc1_r2_S14_L005_R1_001.fastq.gz | miRNA-Seq | 70.3 MB |
| b8p42_hepg2_sh_dkc1_r2_S14_L005_R1_001.fastq.gz | miRNA-Seq | 70.3 MB |
| b8p42_hepg2_sh_larp4_r1_S20_L005_R1_001.fastq.gz | miRNA-Seq | 117.8 MB |
| b8p42_hepg2_sh_larp4_r1_S20_L005_R1_001.fastq.gz | miRNA-Seq | 117.8 MB |
| b8p42_hepg2_sh_larp4_r2_S35_L005_R1_001.fastq.gz | miRNA-Seq | 154.5 MB |
| b8p42_hepg2_sh_larp4_r2_S35_L005_R1_001.fastq.gz | miRNA-Seq | 154.5 MB |
| b8p42_hepg2_sh_larp7_r1_S39_L005_R1_001.fastq.gz | miRNA-Seq | 107.5 MB |
| b8p42_hepg2_sh_larp7_r1_S39_L005_R1_001.fastq.gz | miRNA-Seq | 107.5 MB |
| b8p42_hepg2_sh_larp7_r2_S38_L005_R1_001.fastq.gz | miRNA-Seq | 125.1 MB |
| b8p42_hepg2_sh_larp7_r2_S38_L005_R1_001.fastq.gz | miRNA-Seq | 125.1 MB |
| b8p42_hepg2_sh_lin28b_r1_S16_L005_R1_001.fastq.gz | miRNA-Seq | 137.0 MB |
| b8p42_hepg2_sh_lin28b_r1_S16_L005_R1_001.fastq.gz | miRNA-Seq | 137.0 MB |
| b8p42_hepg2_sh_lin28b_r2_S44_L005_R1_001.fastq.gz | miRNA-Seq | 207.4 MB |
| b8p42_hepg2_sh_lin28b_r2_S44_L005_R1_001.fastq.gz | miRNA-Seq | 207.4 MB |
| b8p42_hepg2_sh_rbfox2_r1_S13_L005_R1_001.fastq.gz | miRNA-Seq | 135.8 MB |
| b8p42_hepg2_sh_rbfox2_r1_S13_L005_R1_001.fastq.gz | miRNA-Seq | 135.8 MB |
| b8p42_hepg2_sh_rbfox2_r2_S40_L005_R1_001.fastq.gz | miRNA-Seq | 117.1 MB |
| b8p42_hepg2_sh_rbfox2_r2_S40_L005_R1_001.fastq.gz | miRNA-Seq | 117.1 MB |
| b8p42_hepg2_sh_sltm_r1_S21_L005_R1_001.fastq.gz | miRNA-Seq | 127.2 MB |
| b8p42_hepg2_sh_sltm_r1_S21_L005_R1_001.fastq.gz | miRNA-Seq | 127.2 MB |
| b8p42_hepg2_sh_sltm_r2_S37_L005_R1_001.fastq.gz | miRNA-Seq | 102.0 MB |
| b8p42_hepg2_sh_sltm_r2_S37_L005_R1_001.fastq.gz | miRNA-Seq | 102.0 MB |
| b8p42_k562_sh_bud13_r1_S27_L005_R1_001.fastq.gz | miRNA-Seq | 111.7 MB |
| b8p42_k562_sh_bud13_r1_S27_L005_R1_001.fastq.gz | miRNA-Seq | 111.7 MB |
| b8p42_k562_sh_bud13_r2_S25_L005_R1_001.fastq.gz | miRNA-Seq | 105.6 MB |
| b8p42_k562_sh_bud13_r2_S25_L005_R1_001.fastq.gz | miRNA-Seq | 105.6 MB |
| b8p42_k562_sh_control1_r1_S22_L005_R1_001.fastq.gz | miRNA-Seq | 91.1 MB |
| b8p42_k562_sh_control1_r1_S22_L005_R1_001.fastq.gz | miRNA-Seq | 91.1 MB |
| b8p42_k562_sh_control1_r2_S45_L005_R1_001.fastq.gz | miRNA-Seq | 97.9 MB |
| b8p42_k562_sh_control1_r2_S45_L005_R1_001.fastq.gz | miRNA-Seq | 97.9 MB |
| b8p42_k562_sh_control2_r1_S41_L005_R1_001.fastq.gz | miRNA-Seq | 104.0 MB |
| b8p42_k562_sh_control2_r1_S41_L005_R1_001.fastq.gz | miRNA-Seq | 104.0 MB |
| b8p42_k562_sh_control2_r2_S42_L005_R1_001.fastq.gz | miRNA-Seq | 114.0 MB |
| b8p42_k562_sh_control2_r2_S42_L005_R1_001.fastq.gz | miRNA-Seq | 114.0 MB |
| b8p42_k562_sh_ddx3x_r1_S47_L005_R1_001.fastq.gz | miRNA-Seq | 103.8 MB |
| b8p42_k562_sh_ddx3x_r1_S47_L005_R1_001.fastq.gz | miRNA-Seq | 103.8 MB |
| b8p42_k562_sh_ddx3x_r2_S12_L005_R1_001.fastq.gz | miRNA-Seq | 112.0 MB |
| b8p42_k562_sh_ddx3x_r2_S12_L005_R1_001.fastq.gz | miRNA-Seq | 112.0 MB |
| b8p42_k562_sh_dkc1_r1_S23_L005_R1_001.fastq.gz | miRNA-Seq | 100.2 MB |
| b8p42_k562_sh_dkc1_r1_S23_L005_R1_001.fastq.gz | miRNA-Seq | 100.2 MB |
| b8p42_k562_sh_dkc1_r2_S10_L005_R1_001.fastq.gz | miRNA-Seq | 104.4 MB |
| b8p42_k562_sh_dkc1_r2_S10_L005_R1_001.fastq.gz | miRNA-Seq | 104.4 MB |
| b8p42_k562_sh_larp4_r1_S48_L005_R1_001.fastq.gz | miRNA-Seq | 103.3 MB |
| b8p42_k562_sh_larp4_r1_S48_L005_R1_001.fastq.gz | miRNA-Seq | 103.3 MB |
| b8p42_k562_sh_larp4_r2_S17_L005_R1_001.fastq.gz | miRNA-Seq | 103.9 MB |
| b8p42_k562_sh_larp4_r2_S17_L005_R1_001.fastq.gz | miRNA-Seq | 103.9 MB |
| b8p42_k562_sh_larp7_r1_S28_L005_R1_001.fastq.gz | miRNA-Seq | 213.9 MB |
| b8p42_k562_sh_larp7_r1_S28_L005_R1_001.fastq.gz | miRNA-Seq | 213.9 MB |
| b8p42_k562_sh_larp7_r2_S46_L005_R1_001.fastq.gz | miRNA-Seq | 101.6 MB |
| b8p42_k562_sh_larp7_r2_S46_L005_R1_001.fastq.gz | miRNA-Seq | 101.6 MB |
| b8p42_k562_sh_lin28b_r1_S30_L005_R1_001.fastq.gz | miRNA-Seq | 321.1 MB |
| b8p42_k562_sh_lin28b_r1_S30_L005_R1_001.fastq.gz | miRNA-Seq | 321.1 MB |
| b8p42_k562_sh_lin28b_r2_S18_L005_R1_001.fastq.gz | miRNA-Seq | 95.9 MB |
| b8p42_k562_sh_lin28b_r2_S18_L005_R1_001.fastq.gz | miRNA-Seq | 95.9 MB |
| b8p42_k562_sh_rbfox2_r1_S31_L005_R1_001.fastq.gz | miRNA-Seq | 267.2 MB |
| b8p42_k562_sh_rbfox2_r1_S31_L005_R1_001.fastq.gz | miRNA-Seq | 267.2 MB |
| b8p42_k562_sh_rbfox2_r2_S34_L005_R1_001.fastq.gz | miRNA-Seq | 107.0 MB |
| b8p42_k562_sh_sltm_r1_S43_L005_R1_001.fastq.gz | miRNA-Seq | 104.0 MB |
| b8p42_k562_sh_sltm_r1_S43_L005_R1_001.fastq.gz | miRNA-Seq | 104.0 MB |
| b8p42_k562_sh_sltm_r2_S32_L005_R1_001.fastq.gz | miRNA-Seq | 481.9 MB |
| b8p59_smallrnaseq_hepg2_sh_control_1_S17_L008_R1_001.fastq.… | miRNA-Seq | 337.3 MB |
| b8p59_smallrnaseq_hepg2_sh_control_1_S17_L008_R1_001.fastq.… | miRNA-Seq | 337.3 MB |
| b8p59_smallrnaseq_hepg2_sh_control_2_S22_L008_R1_001.fastq.… | miRNA-Seq | 172.0 MB |
| b8p59_smallrnaseq_hepg2_sh_control_2_S22_L008_R1_001.fastq.… | miRNA-Seq | 172.0 MB |
| b8p59_smallrnaseq_hepg2_sh_control_3_S19_L008_R1_001.fastq.… | miRNA-Seq | 242.0 MB |
| b8p59_smallrnaseq_hepg2_sh_control_3_S19_L008_R1_001.fastq.… | miRNA-Seq | 242.0 MB |
| b8p59_smallrnaseq_hepg2_sh_control_4_S24_L008_R1_001.fastq.… | miRNA-Seq | 212.9 MB |
| b8p59_smallrnaseq_hepg2_sh_control_4_S24_L008_R1_001.fastq.… | miRNA-Seq | 212.9 MB |
| b8p59_smallrnaseq_hepg2_sh_hnrnpm_1_S8_L008_R1_001.fastq.gz | miRNA-Seq | 180.7 MB |
| b8p59_smallrnaseq_hepg2_sh_hnrnpm_1_S8_L008_R1_001.fastq.gz | miRNA-Seq | 180.7 MB |
| b8p59_smallrnaseq_hepg2_sh_hnrnpm_2_S9_L008_R1_001.fastq.gz | miRNA-Seq | 819.2 KB |
| b8p59_smallrnaseq_hepg2_sh_hnrnpm_2_S9_L008_R1_001.fastq.gz | miRNA-Seq | 819.2 KB |
| b8p59_smallrnaseq_hepg2_sh_ilf3_1_S2_L008_R1_001.fastq.gz | miRNA-Seq | 317.0 MB |
| b8p59_smallrnaseq_hepg2_sh_ilf3_1_S2_L008_R1_001.fastq.gz | miRNA-Seq | 317.0 MB |
| b8p59_smallrnaseq_hepg2_sh_ilf3_2_S20_L008_R1_001.fastq.gz | miRNA-Seq | 232.1 MB |
| b8p59_smallrnaseq_hepg2_sh_ilf3_2_S20_L008_R1_001.fastq.gz | miRNA-Seq | 232.1 MB |
| b8p59_smallrnaseq_hepg2_sh_prpf8_1_S18_L008_R1_001.fastq.gz | miRNA-Seq | 309.0 MB |
| b8p59_smallrnaseq_hepg2_sh_prpf8_1_S18_L008_R1_001.fastq.gz | miRNA-Seq | 309.0 MB |
| b8p59_smallrnaseq_hepg2_sh_prpf8_2_S16_L008_R1_001.fastq.gz | miRNA-Seq | 240.8 MB |
| b8p59_smallrnaseq_hepg2_sh_prpf8_2_S16_L008_R1_001.fastq.gz | miRNA-Seq | 240.8 MB |
| b8p59_smallrnaseq_hepg2_sh_ptbp1_1_S4_L008_R1_001.fastq.gz | miRNA-Seq | 213.2 MB |
| b8p59_smallrnaseq_hepg2_sh_ptbp1_1_S4_L008_R1_001.fastq.gz | miRNA-Seq | 213.2 MB |
| b8p59_smallrnaseq_hepg2_sh_ptbp1_2_S5_L008_R1_001.fastq.gz | miRNA-Seq | 184.3 MB |
| b8p59_smallrnaseq_hepg2_sh_ptbp1_2_S5_L008_R1_001.fastq.gz | miRNA-Seq | 184.3 MB |
| b8p59_smallrnaseq_hepg2_sh_sf3b4_1_S6_L008_R1_001.fastq.gz | miRNA-Seq | 270.5 MB |
| b8p59_smallrnaseq_hepg2_sh_sf3b4_1_S6_L008_R1_001.fastq.gz | miRNA-Seq | 270.5 MB |
| b8p59_smallrnaseq_hepg2_sh_sf3b4_2_S7_L008_R1_001.fastq.gz | miRNA-Seq | 187.8 MB |
| b8p59_smallrnaseq_hepg2_sh_sf3b4_2_S7_L008_R1_001.fastq.gz | miRNA-Seq | 187.8 MB |
| b8p59_smallrnaseq_k562_sh_control_1_S25_L008_R1_001.fastq.gz | miRNA-Seq | 311.8 MB |
| b8p59_smallrnaseq_k562_sh_control_1_S25_L008_R1_001.fastq.gz | miRNA-Seq | 311.8 MB |
| b8p59_smallrnaseq_k562_sh_control_2_S26_L008_R1_001.fastq.gz | miRNA-Seq | 170.6 MB |
| b8p59_smallrnaseq_k562_sh_control_2_S26_L008_R1_001.fastq.gz | miRNA-Seq | 170.6 MB |
| b8p59_smallrnaseq_k562_sh_control_3_S1_L008_R1_001.fastq.gz | miRNA-Seq | 185.9 MB |
| b8p59_smallrnaseq_k562_sh_control_3_S1_L008_R1_001.fastq.gz | miRNA-Seq | 185.9 MB |
| b8p59_smallrnaseq_k562_sh_control_4_S3_L008_R1_001.fastq.gz | miRNA-Seq | 178.5 MB |
| b8p59_smallrnaseq_k562_sh_control_4_S3_L008_R1_001.fastq.gz | miRNA-Seq | 178.5 MB |
| b8p59_smallrnaseq_k562_sh_hnrnpm_1_S11_L008_R1_001.fastq.gz | miRNA-Seq | 181.2 MB |
| b8p59_smallrnaseq_k562_sh_hnrnpm_1_S11_L008_R1_001.fastq.gz | miRNA-Seq | 181.2 MB |
| b8p59_smallrnaseq_k562_sh_hnrnpm_2_S12_L008_R1_001.fastq.gz | miRNA-Seq | 178.8 MB |
| b8p59_smallrnaseq_k562_sh_hnrnpm_2_S12_L008_R1_001.fastq.gz | miRNA-Seq | 178.8 MB |
| b8p59_smallrnaseq_k562_sh_ilf3_1_S13_L008_R1_001.fastq.gz | miRNA-Seq | 184.7 MB |
| b8p59_smallrnaseq_k562_sh_ilf3_1_S13_L008_R1_001.fastq.gz | miRNA-Seq | 184.7 MB |
| b8p59_smallrnaseq_k562_sh_ilf3_2_S14_L008_R1_001.fastq.gz | miRNA-Seq | 266.3 MB |
| b8p59_smallrnaseq_k562_sh_ilf3_2_S14_L008_R1_001.fastq.gz | miRNA-Seq | 266.3 MB |
| b8p59_smallrnaseq_k562_sh_prpf8_1_S10_L008_R1_001.fastq.gz | miRNA-Seq | 204.8 KB |
| b8p59_smallrnaseq_k562_sh_prpf8_1_S10_L008_R1_001.fastq.gz | miRNA-Seq | 204.8 KB |
| b8p59_smallrnaseq_k562_sh_prpf8_2_S15_L008_R1_001.fastq.gz | miRNA-Seq | 188.3 MB |
| b8p59_smallrnaseq_k562_sh_prpf8_2_S15_L008_R1_001.fastq.gz | miRNA-Seq | 188.3 MB |
| b8p59_smallrnaseq_k562_sh_ptbp1_1_S23_L008_R1_001.fastq.gz | miRNA-Seq | 187.2 MB |
| b8p59_smallrnaseq_k562_sh_ptbp1_1_S23_L008_R1_001.fastq.gz | miRNA-Seq | 187.2 MB |
| b8p59_smallrnaseq_k562_sh_ptbp1_2_S27_L008_R1_001.fastq.gz | miRNA-Seq | 167.3 MB |
| b8p59_smallrnaseq_k562_sh_ptbp1_2_S27_L008_R1_001.fastq.gz | miRNA-Seq | 167.3 MB |
| b8p59_smallrnaseq_k562_sh_sf3b4_1_S28_L008_R1_001.fastq.gz | miRNA-Seq | 179.7 MB |
| b8p59_smallrnaseq_k562_sh_sf3b4_1_S28_L008_R1_001.fastq.gz | miRNA-Seq | 179.7 MB |
| b8p59_smallrnaseq_k562_sh_sf3b4_2_S21_L008_R1_001.fastq.gz | miRNA-Seq | 121.7 MB |
| b8p59_smallrnaseq_k562_sh_sf3b4_2_S21_L008_R1_001.fastq.gz | miRNA-Seq | 121.7 MB |
| SRR5925702 | miRNA-Seq | 107.0 MB |
| SRR5925704 | miRNA-Seq | 481.9 MB |
Analysis Pipelines (1)
GSE102497 eCLIP Data Processing
5 steps