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Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels.

Julia K Nussbacher, Gene W Yeo

Molecular cell · 2018 · Vol. 69 (6) · pp. 1005-1016.e7

PubMed ↗ DOI ↗ PMC full text ↗

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.

Linked datasets 1

GSE102497 GSE · via ncbi_elink
GEO ↗

Systematic discovery of RNA binding proteins that control microRNA processing

Homo sapiens

138 data files
FileTypeSize
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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_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_2_S21_L008_R1_001.fastq.gz miRNA-Seq 121.7 MB
SRR5925665_GSM2739595 miRNA-Seq 113.0 MB
SRR5925666_GSM2739596 miRNA-Seq 133.0 MB
SRR5925667_GSM2739597 miRNA-Seq 120.0 MB
SRR5925668_GSM2739598 miRNA-Seq 179.0 MB
SRR5925669_GSM2739599 miRNA-Seq 118.0 MB
SRR5925670_GSM2739600 miRNA-Seq 108.0 MB
SRR5925671_GSM2739601 miRNA-Seq 135.0 MB
SRR5925672_GSM2739602 miRNA-Seq 131.0 MB
SRR5925673_GSM2739603 miRNA-Seq 167.0 MB
SRR5925674_GSM2739604 miRNA-Seq 70.0 MB
SRR5925675_GSM2739605 miRNA-Seq 117.0 MB
SRR5925676_GSM2739606 miRNA-Seq 154.0 MB
SRR5925677_GSM2739607 miRNA-Seq 107.0 MB
SRR5925678_GSM2739608 miRNA-Seq 125.0 MB
SRR5925679_GSM2739609 miRNA-Seq 137.0 MB
SRR5925680_GSM2739610 miRNA-Seq 207.0 MB
SRR5925681_GSM2739611 miRNA-Seq 135.0 MB
SRR5925682_GSM2739612 miRNA-Seq 117.0 MB
SRR5925683_GSM2739613 miRNA-Seq 127.0 MB
SRR5925684_GSM2739614 miRNA-Seq 102.0 MB
SRR5925685_GSM2739615 miRNA-Seq 111.0 MB
SRR5925686_GSM2739616 miRNA-Seq 105.0 MB
SRR5925687_GSM2739617 miRNA-Seq 91.0 MB
SRR5925688_GSM2739618 miRNA-Seq 97.0 MB
SRR5925689_GSM2739619 miRNA-Seq 104.0 MB
SRR5925690_GSM2739620 miRNA-Seq 113.0 MB
SRR5925691_GSM2739621 miRNA-Seq 103.0 MB
SRR5925692_GSM2739622 miRNA-Seq 112.0 MB
SRR5925693_GSM2739623 miRNA-Seq 100.0 MB
SRR5925694_GSM2739624 miRNA-Seq 104.0 MB
SRR5925695_GSM2739625 miRNA-Seq 103.0 MB
SRR5925696_GSM2739626 miRNA-Seq 103.0 MB
SRR5925697_GSM2739627 miRNA-Seq 213.0 MB
SRR5925698_GSM2739628 miRNA-Seq 101.0 MB
SRR5925699_GSM2739629 miRNA-Seq 321.0 MB
SRR5925700_GSM2739630 miRNA-Seq 95.0 MB
SRR5925701_GSM2739631 miRNA-Seq 267.0 MB
SRR5925702 miRNA-Seq 107.0 MB
SRR5925702_GSM2739632 miRNA-Seq 106.0 MB
SRR5925703_GSM2739633 miRNA-Seq 104.0 MB
SRR5925704 miRNA-Seq 481.9 MB
SRR5925704_GSM2739634 miRNA-Seq 481.0 MB
SRR5925705_GSM2739635 miRNA-Seq 337.0 MB
SRR5925706_GSM2739636 miRNA-Seq 172.0 MB
SRR5925707_GSM2739637 miRNA-Seq 241.0 MB
SRR5925708_GSM2739638 miRNA-Seq 212.0 MB
SRR5925709_GSM2739639 miRNA-Seq 180.0 MB
SRR5925710_GSM2739640 miRNA-Seq
SRR5925711_GSM2739641 miRNA-Seq 316.0 MB
SRR5925712_GSM2739642 miRNA-Seq 232.0 MB
SRR5925713_GSM2739643 miRNA-Seq 309.0 MB
SRR5925714_GSM2739644 miRNA-Seq 240.0 MB
SRR5925715_GSM2739645 miRNA-Seq 213.0 MB
SRR5925716_GSM2739646 miRNA-Seq 184.0 MB
SRR5925717_GSM2739647 miRNA-Seq 270.0 MB
SRR5925718_GSM2739648 miRNA-Seq 187.0 MB
SRR5925719_GSM2739649 miRNA-Seq 311.0 MB
SRR5925720_GSM2739650 miRNA-Seq 170.0 MB
SRR5925721_GSM2739651 miRNA-Seq 185.0 MB
SRR5925722_GSM2739652 miRNA-Seq 178.0 MB
SRR5925723_GSM2739653 miRNA-Seq 181.0 MB
SRR5925724_GSM2739654 miRNA-Seq 178.0 MB
SRR5925725_GSM2739655 miRNA-Seq 184.0 MB
SRR5925726_GSM2739656 miRNA-Seq 266.0 MB
SRR5925727_GSM2739657 miRNA-Seq
SRR5925728_GSM2739658 miRNA-Seq 188.0 MB
SRR5925729_GSM2739659 miRNA-Seq 187.0 MB
SRR5925730_GSM2739660 miRNA-Seq 167.0 MB
SRR5925731_GSM2739661 miRNA-Seq 179.0 MB
SRR5925732_GSM2739662 miRNA-Seq 121.0 MB

Potentially related datasets 1

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
GSE102497 GSE · GEO GEO ↗ Systematic discovery of RNA binding proteins that control microRNA processing

Analysis pipelines 1

Pipeline Assay Steps Dataset
GSE102497 eCLIP Data Processing geo_data_processing eCLIP 5 GSE102497
Funding 3 grants
Grant Funder
R01 HG004659 NHGRI NIH HHS (United States)
T32 CA067754 NCI NIH HHS (United States)
U54 HG007005 NHGRI NIH HHS (United States)