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Non-microRNA binding competitively inhibits LIN28 regulation.

Frederick E Tan, Shashank Sathe, Emily C Wheeler, Gene W Yeo

Cell reports · 2021 · Vol. 36 (6) · pp. 109517

Abstract

RNA binding protein (RBP) expression is finite. For RBPs that are vastly outnumbered by their potential target sites, a simple competition for binding can set the magnitude of post-transcriptional control. Here, we show that LIN28, best known for its direct regulation of let-7 miRNA biogenesis, is also indirectly regulated by its widespread binding of non-miRNA transcripts. Approximately 99% of LIN28 binding sites are found on non-miRNA transcripts, like protein coding and ribosomal RNAs. These sites are bound specifically and strongly, but they do not appear to mediate direct post-transcriptional regulation. Instead, non-miRNA sites act to sequester LIN28 protein and effectively change its functional availability, thus impeding the regulation of let-7 in cells. Together, these data show that the binding properties of the transcriptome broadly influence the ability of an RBP to mediate changes in RNA metabolism and gene expression.

Linked datasets 2

GSE109423 GSE · via ncbi_elink
GEO ↗

A transcriptome-wide divergence in protein translation scales with LIN28B expression

Mus musculus

71 data files
FileTypeSize
b8p100_smallrnaseq_hek293_ko_l7_ip_S27_L002_R1_001.fastq.gz RIP-Seq 335.9 MB
b8p100_smallrnaseq_hek293_ko_l7_total_S23_L002_R1_001.fastq… ncRNA-Seq 457.6 MB
b8p100_smallrnaseq_hek293_ko_wt_ip_S25_L002_R1_001.fastq.gz RIP-Seq 304.6 MB
b8p100_smallrnaseq_hek293_ko_wt_total_S21_L002_R1_001.fastq… ncRNA-Seq 563.8 MB
b8p100_smallrnaseq_hek293_x3_l7_ip_S28_L002_R1_001.fastq.gz RIP-Seq 241.0 MB
b8p100_smallrnaseq_hek293_x3_l7_total_S24_L002_R1_001.fastq… ncRNA-Seq 509.1 MB
b8p100_smallrnaseq_hek293_x3_wt_ip_S26_L002_R1_001.fastq.gz RIP-Seq 341.6 MB
b8p100_smallrnaseq_hek293_x3_wt_total_S22_L002_R1_001.fastq… ncRNA-Seq 617.8 MB
b8p37_a9_input_let7_S1_L003_R1_001.fastq.gz RNA-Seq 857.6 MB
b8p37_a9_input_S11_L004_R1_001.fastq.gz RNA-Seq 912.5 MB
b8p37_a9_polysome_let7_S6_L003_R1_001.fastq.gz OTHER 274.7 MB
b8p37_a9_polysome_S16_L004_R1_001.fastq.gz OTHER 279.9 MB
b8p37_x1_input_S12_L004_R1_001.fastq.gz RNA-Seq 862.4 MB
b8p37_x1_polysome_S17_L004_R1_001.fastq.gz OTHER 284.3 MB
b8p37_x2_input_S13_L004_R1_001.fastq.gz RNA-Seq 1.2 GB
b8p37_x2_polysome_S18_L004_R1_001.fastq.gz OTHER 214.5 MB
b8p37_x3_input_S14_L004_R1_001.fastq.gz RNA-Seq 1.2 GB
b8p37_x3_polysome_S19_L004_R1_001.fastq.gz OTHER 344.3 MB
b8p37_x4_input_S15_L004_R1_001.fastq.gz RNA-Seq 987.2 MB
b8p37_x4_polysome_S20_L004_R1_001.fastq.gz OTHER 255.7 MB
PX0_S52_L006_R1_001.fastq.gz OTHER 1.8 GB
PX1_S53_L006_R1_001.fastq.gz OTHER 1.5 GB
PX2_S54_L006_R1_001.fastq.gz OTHER 1.7 GB
PX3_S55_L006_R1_001.fastq.gz OTHER 1.7 GB
PX4_S56_L006_R1_001.fastq.gz OTHER 1.5 GB
PX4_S56_L006_R2_001.fastq.gz OTHER 1.5 GB
SRR6497056_GSM2942714 OTHER 279.0 MB
SRR6497057_GSM2942715 OTHER 284.0 MB
SRR6497058 OTHER 214.5 MB
SRR6497058_GSM2942716 OTHER 214.0 MB
SRR6497059 OTHER 344.3 MB
SRR6497059_GSM2942717 OTHER 344.0 MB
SRR6497060 OTHER 255.7 MB
SRR6497060_GSM2942718 OTHER 255.0 MB
SRR6497061_GSM2942719 RNA-Seq 912.0 MB
SRR6497062_GSM2942720 RNA-Seq 862.0 MB
SRR6497063_GSM2942721 RNA-Seq 1.2 GB
SRR6497064_GSM2942722 RNA-Seq 1.2 GB
SRR6497065_GSM2942723 RNA-Seq 987.0 MB
SRR6497066_GSM2942724 OTHER 1.8 GB
SRR6497067_GSM2942725 OTHER 1.5 GB
SRR6497068_GSM2942726 OTHER 1.7 GB
SRR6497069_GSM2942727 OTHER 1.7 GB
SRR6497070_GSM2942728 OTHER 1.5 GB
SRR6497071 RNA-Seq 2.0 GB
SRR6497071_GSM2942729 RNA-Seq 2.0 GB
SRR6497072_GSM2942730 RNA-Seq 1.4 GB
SRR6497073_GSM2942731 RNA-Seq 1.3 GB
SRR6497074 RNA-Seq 1.6 GB
SRR6497074_GSM2942732 RNA-Seq 1.6 GB
SRR6497075 RNA-Seq 1.8 GB
SRR6497075_GSM2942733 RNA-Seq 1.8 GB
SRR6497076_GSM2942734 RIP-Seq 335.0 MB
SRR6497077_GSM2942735 ncRNA-Seq 457.0 MB
SRR6497078_GSM2942736 RIP-Seq 304.0 MB
SRR6497079 ncRNA-Seq 563.8 MB
SRR6497079_GSM2942737 ncRNA-Seq 563.0 MB
SRR6497080_GSM2942738 RIP-Seq 241.0 MB
SRR6497081 ncRNA-Seq 509.1 MB
SRR6497081_GSM2942739 ncRNA-Seq 509.0 MB
SRR6497082_GSM2942740 RIP-Seq 341.0 MB
SRR6497083 ncRNA-Seq 617.8 MB
SRR6497083_GSM2942741 ncRNA-Seq 617.0 MB
SRR6497084_GSM2942742 OTHER 274.0 MB
SRR6497085 RNA-Seq 857.6 MB
SRR6497085_GSM2942743 RNA-Seq 857.0 MB
TX0_S47_L006_R1_001.fastq.gz RNA-Seq 2.0 GB
TX1_S48_L006_R1_001.fastq.gz RNA-Seq 1.4 GB
TX2_S49_L006_R1_001.fastq.gz RNA-Seq 1.3 GB
TX3_S50_L006_R1_001.fastq.gz RNA-Seq 1.6 GB
TX4_S51_L006_R1_001.fastq.gz RNA-Seq 1.8 GB
GSE178259 GSE · via ncbi_elink
GEO ↗

Non-microRNA Binding Competitively Inhibits LIN28 Regulation

Mus musculus

76 data files
FileTypeSize
dd-Cit-P-1_S5_L007_R1_001.fastq.gz RNA-Seq 1.2 GB
dd-Cit-P-2_S6_L007_R1_001.fastq.gz RNA-Seq 1.3 GB
dd-Cit-T-1_S1_L007_R1_001.fastq.gz RNA-Seq 1.1 GB
dd-Cit-T-2_S2_L007_R1_001.fastq.gz RNA-Seq 1.4 GB
dd-HpK-P-1_S7_L007_R1_001.fastq.gz RNA-Seq 1.2 GB
dd-HpK-P-2_S8_L007_R1_001.fastq.gz RNA-Seq 1.2 GB
dd-HpK-T-1_S3_L007_R1_001.fastq.gz RNA-Seq 1.5 GB
dd-HpK-T-2_S4_L007_R1_001.fastq.gz RNA-Seq 1.6 GB
HPK_mESCs_IN7_mock_R1_merged.fastq.gz RNA-Seq 1.2 GB
HPK_mESCs_IP3_mock_S20_L007_R1_001.fastq.gz RNA-Seq 1.4 GB
HPK_mESCs_IP7_mock_R1_merged.fastq.gz RNA-Seq 1.2 GB
Hpk_mock_1_poly_S7_L001_R1_001.fastq.gz RNA-Seq 793.0 MB
Hpk_mock_1_S5_L001_R1_001.fastq.gz RNA-Seq 927.7 MB
Hpk_mock_2_poly_S19_L002_R1_001.fastq.gz RNA-Seq 842.0 MB
Hpk_mock_2_S17_L002_R1_001.fastq.gz RNA-Seq 874.2 MB
LIN28B_PHI_1_CLIP_R1_S32_L002_R1_A01_B06.fastq.gz RNA-Seq 460.8 MB
LIN28B_PHI_1_CLIP_R2_S24_L002_R1_A01_B06.fastq.gz RNA-Seq 305.6 MB
LIN28B_PHI_1_INPUT_R1_S29_L002_R1.fastq.gz RNA-Seq 1.2 GB
LIN28B_PHI_1_INPUT_R2_S21_L002_R1.fastq.gz RNA-Seq 786.1 MB
LIN28B_PHI_2_CLIP_R1_S31_L002_R1_C01_D08.fastq.gz RNA-Seq 420.8 MB
LIN28B_PHI_2_CLIP_R2_S23_L002_R1_C01_D08.fastq.gz RNA-Seq 361.7 MB
LIN28B_PHI_2_INPUT_R1_S30_L002_R1.fastq.gz RNA-Seq 1.1 GB
LIN28B_PHI_2_INPUT_R2_S22_L002_R1.fastq.gz RNA-Seq 1009.7 MB
LIN28B_PHI_3_CLIP_R1_S28_L002_R1_A04_F05.fastq.gz RNA-Seq 439.3 MB
LIN28B_PHI_3_CLIP_R2_S20_L002_R1_A04_F05.fastq.gz RNA-Seq 425.0 MB
LIN28B_PHI_3_INPUT_R1_S25_L002_R1.fastq.gz RNA-Seq 715.9 MB
LIN28B_PHI_3_INPUT_R2_S17_L002_R1.fastq.gz RNA-Seq 1.0 GB
LIN28B_PHI_4_CLIP_R1_S27_L002_R1_X2A_X2B.fastq.gz RNA-Seq 445.6 MB
LIN28B_PHI_4_CLIP_R2_S19_L002_R1_X2A_X2B.fastq.gz RNA-Seq 783.6 MB
LIN28B_PHI_4_INPUT_R1_S26_L002_R1.fastq.gz RNA-Seq 1.1 GB
LIN28B_PHI_4_INPUT_R2_S18_L002_R1.fastq.gz RNA-Seq 958.2 MB
SRR14820418_GSM5385970 RNA-Seq 1.2 GB
SRR14820419_GSM5385971 RNA-Seq 1.3 GB
SRR14820420_GSM5385972 RNA-Seq 1.1 GB
SRR14820421_GSM5385973 RNA-Seq 1.4 GB
SRR14820422_GSM5385974 RNA-Seq 1.2 GB
SRR14820423_GSM5385975 RNA-Seq 1.2 GB
SRR14820424_GSM5385976 RNA-Seq 1.5 GB
SRR14820425_GSM5385977 RNA-Seq 1.6 GB
SRR14820426_GSM5385978 RNA-Seq 927.0 MB
SRR14820427_GSM5385979 RNA-Seq 793.0 MB
SRR14820428_GSM5385980 RNA-Seq 874.0 MB
SRR14820429_GSM5385981 RNA-Seq 841.0 MB
SRR14820430_GSM5385982 RNA-Seq 860.0 MB
SRR14820431_GSM5385983 RNA-Seq 785.0 MB
SRR14820432_GSM5385984 RNA-Seq 874.0 MB
SRR14820433_GSM5385985 RNA-Seq 910.0 MB
SRR14820434_GSM5385986 RNA-Seq 1.2 GB
SRR14820435_GSM5385987 RNA-Seq 1.4 GB
SRR14820436_GSM5385988 RNA-Seq 1.2 GB
SRR14820437_GSM5385989 RNA-Seq 1.1 GB
SRR14820438_GSM5385990 RNA-Seq 1.1 GB
SRR14820439_GSM5385991 RNA-Seq 1.4 GB
SRR14820440_GSM5385992 RNA-Seq 460.0 MB
SRR14820441_GSM5385993 RNA-Seq 305.0 MB
SRR14820442_GSM5385994 RNA-Seq 420.0 MB
SRR14820443_GSM5385995 RNA-Seq 361.0 MB
SRR14820444_GSM5385996 RNA-Seq 439.0 MB
SRR14820445_GSM5385997 RNA-Seq 424.0 MB
SRR14820446_GSM5385998 RNA-Seq 445.0 MB
SRR14820447_GSM5385999 RNA-Seq 783.0 MB
SRR14820448_GSM5386000 RNA-Seq 1.2 GB
SRR14820449_GSM5386001 RNA-Seq 786.0 MB
SRR14820450_GSM5386002 RNA-Seq 1.1 GB
SRR14820451_GSM5386003 RNA-Seq 1009.0 MB
SRR14820452_GSM5386004 RNA-Seq 715.0 MB
SRR14820453_GSM5386005 RNA-Seq 1.0 GB
SRR14820454_GSM5386006 RNA-Seq 1.1 GB
SRR14820455_GSM5386007 RNA-Seq 958.0 MB
V6_5_mESCs_IN1_mock_R1_merged.fastq.gz RNA-Seq 1.1 GB
V6_5_mESCs_IP1_mock_S19_L007_R1_001.fastq.gz RNA-Seq 1.1 GB
V6_5_mESCs_IP5_mock_S21_L007_R1_001.fastq.gz RNA-Seq 1.4 GB
V6_5_mock_1_poly_S3_L001_R1_001.fastq.gz RNA-Seq 785.1 MB
V6_5_mock_1_S1_L001_R1_001.fastq.gz RNA-Seq 860.6 MB
V6_5_mock_2_poly_S15_L002_R1_001.fastq.gz RNA-Seq 910.9 MB
V6_5_mock_2_S13_L002_R1_001.fastq.gz RNA-Seq 874.1 MB

Potentially related datasets 2

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
GSE109423 GSE · GEO GEO ↗ A transcriptome-wide divergence in protein translation scales with LIN28B expression
GSE178259 GSE · GEO GEO ↗ Non-microRNA Binding Competitively Inhibits LIN28 Regulation

Analysis pipelines 1

Pipeline Assay Steps Dataset
GSE178259 eCLIP Data Processing geo_data_processing eCLIP 6 GSE178259
Funding 3 grants
Grant Funder
R01 HG004659 NHGRI NIH HHS (United States)
T32 GM008666 NIGMS NIH HHS (United States)
U54 HG007005 NHGRI NIH HHS (United States)