A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.
Frederick E Tan, Shashank Sathe, Emily C Wheeler, Julia K Nussbacher, Samson Peter, Gene W Yeo
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.
Linked datasets 1
A transcriptome-wide divergence in protein translation scales with LIN28B expression
Mus musculus
71 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_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 |
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.
Analysis pipelines 1
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE109423 eCLIP Data Processing geo_data_processing | eCLIP | 6 | GSE109423 |
Funding 5 grants
| Grant | Funder |
|---|---|
| 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) |