Large-scale map of RNA-binding protein interactomes across the mRNA life cycle.
Lena A Street, Katherine L Rothamel, Kristopher W Brannan, Wenhao Jin, Benjamin J Bokor, Kevin Dong, Kevin Rhine, Assael Madrigal, Norah Al-Azzam, Jenny Kim Kim, Yanzhe Ma, Darvesh Gorhe, Ahmed Abdou, Erica Wolin, Orel Mizrahi, Joshua Ahdout, Mayuresh Mujumdar, Ella Doron-Mandel, Marko Jovanovic, Gene W Yeo
Molecular cell · 2024 · Vol. 84 (19) · pp. 3790-3809.e8
Abstract
mRNAs interact with RNA-binding proteins (RBPs) throughout their processing and maturation. While efforts have assigned RBPs to RNA substrates, less exploration has leveraged protein-protein interactions (PPIs) to study proteins in mRNA life-cycle stages. We generated an RNA-aware, RBP-centric PPI map across the mRNA life cycle in human cells by immunopurification-mass spectrometry (IP-MS) of ∼100 endogenous RBPs with and without RNase, augmented by size exclusion chromatography-mass spectrometry (SEC-MS). We identify 8,742 known and 20,802 unreported interactions between 1,125 proteins and determine that 73% of the IP-MS-identified interactions are RNA regulated. Our interactome links many proteins, some with unknown functions, to specific mRNA life-cycle stages, with nearly half associated with multiple stages. We demonstrate the value of this resource by characterizing the splicing and export functions of enhancer of rudimentary homolog (ERH), and by showing that small nuclear ribonucleoprotein U5 subunit 200 (SNRNP200) interacts with stress granule proteins and binds cytoplasmic RNA differently during stress.
Linked datasets 1
Large-scale map of RNA binding protein interactomes across the mRNA life-cycle
Homo sapiens
50 data files
| File | Type | Size |
|---|---|---|
| CAPRIN_US_IN1_S164_L001_R1_001.fastq.gz | RIP-Seq | 445.5 MB |
| CAPRIN_US_IN2_S165_L001_R1_001.fastq.gz | RIP-Seq | 552.8 MB |
| CAPRIN_US_IP1_S172_L001_R1_001.fastq.gz | RIP-Seq | 558.7 MB |
| CAPRIN_US_IP2_S173_L001_R1_001.fastq.gz | RIP-Seq | 581.9 MB |
| HEK-baseline-SNRNP200-Input_S22_L002_R1_001.fastq.gz | RIP-Seq | 930.2 MB |
| HEK-baseline-SNRNP200-IP_S23_L002_R1_001.fastq.gz | RIP-Seq | 1.0 GB |
| HEK-Input-SNRNP200_S15_L001_R1_001.fastq.gz | RIP-Seq | 575.7 MB |
| HEK-IP-SNRNP200_S16_L001_R1_001.fastq.gz | RIP-Seq | 535.0 MB |
| HEK-Stress-Input-SNRNP200_S3_L001_R1_001.fastq.gz | RIP-Seq | 523.6 MB |
| HEK-Stress-IP-SNRNP200_S4_L001_R1_001.fastq.gz | RIP-Seq | 642.9 MB |
| HEK-stress-SNRNP200-Input_S26_L002_R1_001.fastq.gz | RIP-Seq | 923.0 MB |
| HEK-stress-SNRNP200-IP_S27_L002_R1_001.fastq.gz | RIP-Seq | 831.6 MB |
| KR-A-IN_S50_L002_R1_001.fastq.gz | RIP-Seq | 354.2 MB |
| KR-A-IP_S49_L002_R1_001.fastq.gz | RIP-Seq | 143.5 MB |
| KR-B-IN_S52_L002_R1_001.fastq.gz | RIP-Seq | 306.5 MB |
| KR-B-IP_S51_L002_R1_001.fastq.gz | RIP-Seq | 293.1 MB |
| SNRNP200_cytoplasmic_arsenite_in1_S156_L001_R1_001.fastq.gz | RIP-Seq | 879.6 MB |
| SNRNP200_cytoplasmic_arsenite_in2_S158_L001_R1_001.fastq.gz | RIP-Seq | 927.3 MB |
| SNRNP200_cytoplasmic_arsenite_ip1_S157_L001_R1_001.fastq.gz | RIP-Seq | 965.0 MB |
| SNRNP200_cytoplasmic_arsenite_ip2_S159_L001_R1_001.fastq.gz | RIP-Seq | 1.0 GB |
| SNRNP200_cytoplasmic_control_in1_S152_L001_R1_001.fastq.gz | RIP-Seq | 673.7 MB |
| SNRNP200_cytoplasmic_control_in2_S154_L001_R1_001.fastq.gz | RIP-Seq | 662.6 MB |
| SNRNP200_cytoplasmic_control_ip1_S153_L001_R1_001.fastq.gz | RIP-Seq | 733.5 MB |
| SNRNP200_cytoplasmic_control_ip2_S155_L001_R1_001.fastq.gz | RIP-Seq | 636.9 MB |
| SRR24321506_GSM7233019 | RIP-Seq | 1.0 GB |
| SRR24321506.lite | RIP-Seq | 1.0 GB |
| SRR24321507_GSM7233018 | RIP-Seq | 964.0 MB |
| SRR24321507.lite | RIP-Seq | 965.0 MB |
| SRR24321508_GSM7233017 | RIP-Seq | 831.0 MB |
| SRR24321509_GSM7233016 | RIP-Seq | 642.0 MB |
| SRR24321510_GSM7233015 | RIP-Seq | 293.0 MB |
| SRR24321511_GSM7233014 | RIP-Seq | 143.0 MB |
| SRR24321512_GSM7233013 | RIP-Seq | 581.0 MB |
| SRR24321513_GSM7233012 | RIP-Seq | 558.0 MB |
| SRR24321514_GSM7233011 | RIP-Seq | 636.0 MB |
| SRR24321515_GSM7233010 | RIP-Seq | 733.0 MB |
| SRR24321516_GSM7233009 | RIP-Seq | 1.0 GB |
| SRR24321517_GSM7233008 | RIP-Seq | 534.0 MB |
| SRR24321518_GSM7233007 | RIP-Seq | 927.0 MB |
| SRR24321519_GSM7233006 | RIP-Seq | 879.0 MB |
| SRR24321520_GSM7233005 | RIP-Seq | 923.0 MB |
| SRR24321521_GSM7233004 | RIP-Seq | 523.0 MB |
| SRR24321522_GSM7233003 | RIP-Seq | 306.0 MB |
| SRR24321523_GSM7233002 | RIP-Seq | 354.0 MB |
| SRR24321524_GSM7233001 | RIP-Seq | 552.0 MB |
| SRR24321525_GSM7233000 | RIP-Seq | 445.0 MB |
| SRR24321526_GSM7232999 | RIP-Seq | 662.0 MB |
| SRR24321527_GSM7232998 | RIP-Seq | 673.0 MB |
| SRR24321528_GSM7232997 | RIP-Seq | 930.0 MB |
| SRR24321529_GSM7232996 | RIP-Seq | 575.0 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 |
|---|---|---|
| MSV000093915 | MASSIVE · MassIVE | No title in the index |
| GSE230717 | GSE · GEO GEO ↗ | Large-scale map of RNA binding protein interactomes across the mRNA life-cycle |
Analysis pipelines 1
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE230717 eCLIP Data Processing geo_data_processing | eCLIP | 9 | GSE230717 |
Funding 11 grants
| Grant | Funder |
|---|---|
| U24 HG009889 | NHGRI NIH HHS (United States) |
| R01 HG004659 | NHGRI NIH HHS (United States) |
| RF1 MH126719 | NIMH NIH HHS (United States) |
| R01 HG011864 | NHGRI NIH HHS (United States) |
| T32 CA067754 | NCI NIH HHS (United States) |
| R01 HG012216 | NHGRI NIH HHS (United States) |
| R35 GM128802 | NIGMS NIH HHS (United States) |
| R01 AG071869 | NIA NIH HHS (United States) |
| R01 CA284315 | NCI NIH HHS (United States) |
| K22 NS112678 | NINDS NIH HHS (United States) |
| K99 NS135103 | NINDS NIH HHS (United States) |