A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.
Molecular cell
· 2019
· Vol. 73
(2)
· pp. 304-313.e3
Abstract
LIN28 RNA binding proteins are dynamically expressed throughout mammalian development and during disease. However, it remains unclear how changes in LIN28 expression define patterns of post-transcriptional gene regulation. Here we show that LIN28 expression level is a key variable that sets the magnitude of protein translation. By systematically varying LIN28B protein levels in human cells, we discovered a dose-dependent divergence in transcriptome-wide ribosome occupancy that enabled the formation of two discrete translational subpopulations composed of nearly all expressed genes. This bifurcation in gene expression was mediated by a redistribution in Argonaute association, from let-7 to non-let-7 microRNA families, resulting in a global shift in cellular miRNA activity. Post-transcriptional effects were scaled across the physiological LIN28 expression range. Together, these data highlight the central importance of RBP expression level and its ability to encode regulation.
Publication Types
["Journal Article", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't"]
MeSH Terms
["Animals", "Argonaute Proteins", "Binding Sites", "Binding, Competitive", "DNA-Binding Proteins", "Gene Expression Regulation", "HEK293 Cells", "Humans", "Mice", "MicroRNAs", "NIH 3T3 Cells", "Protein Binding", "Protein Biosynthesis", "RNA-Binding Proteins", "Ribosomes", "Transcriptome"]
Funding
R01 HG004659
NHGRI NIH HHS
(United States)
T32 CA067754
NCI NIH HHS
(United States)
U41 HG009889
NHGRI NIH HHS
(United States)
T32 GM008666
NIGMS NIH HHS
(United States)
U54 HG007005
NHGRI NIH HHS
(United States)
Linked Datasets (1)
A transcriptome-wide divergence in protein translation scales with LIN28B expression
Mus musculus150 data files
| File | Type | Size |
|---|---|---|
| b8p100_smallrnaseq_hek293_ko_l7_ip_S27_L002_R1_001.fastq.gz | RIP-Seq | 335.9 MB |
| b8p100_smallrnaseq_hek293_ko_l7_ip_S27_L002_R1_001.fastq.gz | RIP-Seq | 335.9 MB |
| b8p100_smallrnaseq_hek293_ko_l7_ip_S27_L002_R1_001.fastq.gz | RIP-Seq | 335.9 MB |
| b8p100_smallrnaseq_hek293_ko_l7_ip_S27_L002_R1_001.fastq.gz | RIP-Seq | 335.9 MB |
| 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_l7_total_S23_L002_R1_001.fastq… | ncRNA-Seq | 457.6 MB |
| b8p100_smallrnaseq_hek293_ko_l7_total_S23_L002_R1_001.fastq… | ncRNA-Seq | 457.6 MB |
| b8p100_smallrnaseq_hek293_ko_l7_total_S23_L002_R1_001.fastq… | ncRNA-Seq | 457.6 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_ip_S25_L002_R1_001.fastq.gz | RIP-Seq | 304.6 MB |
| b8p100_smallrnaseq_hek293_ko_wt_ip_S25_L002_R1_001.fastq.gz | RIP-Seq | 304.6 MB |
| b8p100_smallrnaseq_hek293_ko_wt_ip_S25_L002_R1_001.fastq.gz | RIP-Seq | 304.6 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_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_ip_S28_L002_R1_001.fastq.gz | RIP-Seq | 241.0 MB |
| b8p100_smallrnaseq_hek293_x3_l7_ip_S28_L002_R1_001.fastq.gz | RIP-Seq | 241.0 MB |
| b8p100_smallrnaseq_hek293_x3_l7_ip_S28_L002_R1_001.fastq.gz | RIP-Seq | 241.0 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_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_ip_S26_L002_R1_001.fastq.gz | RIP-Seq | 341.6 MB |
| b8p100_smallrnaseq_hek293_x3_wt_ip_S26_L002_R1_001.fastq.gz | RIP-Seq | 341.6 MB |
| b8p100_smallrnaseq_hek293_x3_wt_ip_S26_L002_R1_001.fastq.gz | RIP-Seq | 341.6 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 |
| 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_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_input_S11_L004_R1_001.fastq.gz | RNA-Seq | 912.5 MB |
| b8p37_a9_input_S11_L004_R1_001.fastq.gz | RNA-Seq | 912.5 MB |
| b8p37_a9_input_S11_L004_R1_001.fastq.gz | RNA-Seq | 912.5 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_let7_S6_L003_R1_001.fastq.gz | OTHER | 274.7 MB |
| b8p37_a9_polysome_let7_S6_L003_R1_001.fastq.gz | OTHER | 274.7 MB |
| b8p37_a9_polysome_let7_S6_L003_R1_001.fastq.gz | OTHER | 274.7 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_a9_polysome_S16_L004_R1_001.fastq.gz | OTHER | 279.9 MB |
| b8p37_a9_polysome_S16_L004_R1_001.fastq.gz | OTHER | 279.9 MB |
| b8p37_a9_polysome_S16_L004_R1_001.fastq.gz | OTHER | 279.9 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_input_S12_L004_R1_001.fastq.gz | RNA-Seq | 862.4 MB |
| b8p37_x1_input_S12_L004_R1_001.fastq.gz | RNA-Seq | 862.4 MB |
| b8p37_x1_input_S12_L004_R1_001.fastq.gz | RNA-Seq | 862.4 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_x1_polysome_S17_L004_R1_001.fastq.gz | OTHER | 284.3 MB |
| b8p37_x1_polysome_S17_L004_R1_001.fastq.gz | OTHER | 284.3 MB |
| b8p37_x1_polysome_S17_L004_R1_001.fastq.gz | OTHER | 284.3 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_input_S13_L004_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| b8p37_x2_input_S13_L004_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| b8p37_x2_input_S13_L004_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| 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_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_input_S14_L004_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| b8p37_x3_input_S14_L004_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| b8p37_x3_input_S14_L004_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| 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_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_input_S15_L004_R1_001.fastq.gz | RNA-Seq | 987.2 MB |
| b8p37_x4_input_S15_L004_R1_001.fastq.gz | RNA-Seq | 987.2 MB |
| b8p37_x4_input_S15_L004_R1_001.fastq.gz | RNA-Seq | 987.2 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 |
| b8p37_x4_polysome_S20_L004_R1_001.fastq.gz | OTHER | 255.7 MB |
| PX0_S52_L006_R1_001.fastq.gz | OTHER | 1.8 GB |
| PX0_S52_L006_R1_001.fastq.gz | OTHER | 1.8 GB |
| PX0_S52_L006_R1_001.fastq.gz | OTHER | 1.8 GB |
| PX0_S52_L006_R1_001.fastq.gz | OTHER | 1.8 GB |
| PX0_S52_L006_R1_001.fastq.gz | OTHER | 1.8 GB |
| PX1_S53_L006_R1_001.fastq.gz | OTHER | 1.5 GB |
| PX1_S53_L006_R1_001.fastq.gz | OTHER | 1.5 GB |
| PX1_S53_L006_R1_001.fastq.gz | OTHER | 1.5 GB |
| PX1_S53_L006_R1_001.fastq.gz | OTHER | 1.5 GB |
| PX1_S53_L006_R1_001.fastq.gz | OTHER | 1.5 GB |
| PX2_S54_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX2_S54_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX2_S54_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX2_S54_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX2_S54_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX3_S55_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX3_S55_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX3_S55_L006_R1_001.fastq.gz | OTHER | 1.7 GB |
| PX3_S55_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_R1_001.fastq.gz | OTHER | 1.5 GB |
| PX4_S56_L006_R2_001.fastq.gz | OTHER | 1.5 GB |
| PX4_S56_L006_R2_001.fastq.gz | OTHER | 1.5 GB |
| PX4_S56_L006_R2_001.fastq.gz | OTHER | 1.5 GB |
| SRR6497058 | OTHER | 214.5 MB |
| SRR6497058 | OTHER | 214.5 MB |
| SRR6497058 | OTHER | 214.5 MB |
| SRR6497059 | OTHER | 344.3 MB |
| SRR6497059 | OTHER | 344.3 MB |
| SRR6497059 | OTHER | 344.3 MB |
| SRR6497060 | OTHER | 255.7 MB |
| SRR6497060 | OTHER | 255.7 MB |
| SRR6497060 | OTHER | 255.7 MB |
| SRR6497071 | RNA-Seq | 2.0 GB |
| SRR6497071 | RNA-Seq | 2.0 GB |
| SRR6497071 | RNA-Seq | 2.0 GB |
| SRR6497074 | RNA-Seq | 1.6 GB |
| SRR6497074 | RNA-Seq | 1.6 GB |
| SRR6497074 | RNA-Seq | 1.6 GB |
| SRR6497075 | RNA-Seq | 1.8 GB |
| SRR6497075 | RNA-Seq | 1.8 GB |
| SRR6497075 | RNA-Seq | 1.8 GB |
| SRR6497079 | ncRNA-Seq | 563.8 MB |
| SRR6497079 | ncRNA-Seq | 563.8 MB |
| SRR6497079 | ncRNA-Seq | 563.8 MB |
| SRR6497081 | ncRNA-Seq | 509.1 MB |
| SRR6497081 | ncRNA-Seq | 509.1 MB |
| SRR6497081 | ncRNA-Seq | 509.1 MB |
| SRR6497083 | ncRNA-Seq | 617.8 MB |
| SRR6497083 | ncRNA-Seq | 617.8 MB |
| SRR6497083 | ncRNA-Seq | 617.8 MB |
| SRR6497085 | RNA-Seq | 857.6 MB |
| SRR6497085 | RNA-Seq | 857.6 MB |
| SRR6497085 | RNA-Seq | 857.6 MB |
| TX0_S47_L006_R1_001.fastq.gz | RNA-Seq | 2.0 GB |
| TX0_S47_L006_R1_001.fastq.gz | RNA-Seq | 2.0 GB |
| TX1_S48_L006_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| TX1_S48_L006_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| TX1_S48_L006_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| TX1_S48_L006_R1_001.fastq.gz | RNA-Seq | 1.4 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 |
| TX2_S49_L006_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| TX2_S49_L006_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| TX2_S49_L006_R1_001.fastq.gz | RNA-Seq | 1.3 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 |
| TX3_S50_L006_R1_001.fastq.gz | RNA-Seq | 1.6 GB |
| TX4_S51_L006_R1_001.fastq.gz | RNA-Seq | 1.8 GB |
| TX4_S51_L006_R1_001.fastq.gz | RNA-Seq | 1.8 GB |
Analysis Pipelines (1)
GSE109423 eCLIP Data Processing
6 steps