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Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies.

Hugo C Medina-Munoz, Eric Kofman, Pratibha Jagannatha, Evan A Boyle, Tao Yu, Krysten L Jones, Jasmine R Mueller, Grace D Lykins, Andrew T Doudna, Samuel S Park, Steven M Blue, Brodie L Ranzau, Rahul M Kohli, Alexis C Komor, Gene W Yeo

Nature communications · 2024 · Vol. 15 (1) · pp. 875

PubMed ↗ DOI ↗ PMC full text ↗

Abstract

RNA binding proteins (RBPs) are key regulators of RNA processing and cellular function. Technologies to discover RNA targets of RBPs such as TRIBE (targets of RNA binding proteins identified by editing) and STAMP (surveying targets by APOBEC1 mediated profiling) utilize fusions of RNA base-editors (rBEs) to RBPs to circumvent the limitations of immunoprecipitation (CLIP)-based methods that require enzymatic digestion and large amounts of input material. To broaden the repertoire of rBEs suitable for editing-based RBP-RNA interaction studies, we have devised experimental and computational assays in a framework called PRINTER (protein-RNA interaction-based triaging of enzymes that edit RNA) to assess over thirty A-to-I and C-to-U rBEs, allowing us to identify rBEs that expand the characterization of binding patterns for both sequence-specific and broad-binding RBPs. We also propose specific rBEs suitable for dual-RBP applications. We show that the choice between single or multiple rBEs to fuse with a given RBP or pair of RBPs hinges on the editing biases of the rBEs and the binding preferences of the RBPs themselves. We believe our study streamlines and enhances the selection of rBEs for the next generation of RBP-RNA target discovery.

Linked datasets 6

GSE232520 GSE · via ncbi_elink
GEO ↗

Expanded palette of RNA base editors for comprehensive RBP-RNA interactome studies

Homo sapiens

GSE232515 GSE · via ncbi_elink
GEO ↗

Expanded repertoire for RNA-editing-based detection for RNA binding protein interactions (3)

Homo sapiens

10 data files
FileTypeSize
Hugo-E1_S31_L002_R1_001.fastq.gz RNA-Seq 432.5 MB
Hugo-E2_S79_L002_R1_001.fastq.gz RNA-Seq 623.7 MB
Hugo-E3_S80_L002_R1_001.fastq.gz RNA-Seq 571.2 MB
Hugo-E4_S32_L002_R1_001.fastq.gz RNA-Seq 550.4 MB
Hugo-E5_S81_L002_R1_001.fastq.gz RNA-Seq 480.7 MB
Hugo-E6_S82_L002_R1_001.fastq.gz RNA-Seq 515.3 MB
Hugo-E7_S33_L002_R1_001.fastq.gz RNA-Seq 456.3 MB
Hugo-E8_S83_L002_R1_001.fastq.gz RNA-Seq 474.5 MB
Hugo-F1_S84_L002_R1_001.fastq.gz RNA-Seq 504.2 MB
Hugo-F2_S34_L002_R1_001.fastq.gz RNA-Seq 498.8 MB
GSE232514 GSE · via ncbi_elink
GEO ↗

Expanded repertoire of RNA-editing-based detection for RNA binding protein interactions (2)

Homo sapiens

10 data files
FileTypeSize
HM-OT-10_S10_L001_R1_001.fastq.gz RNA-Seq 813.2 MB
HM-OT-11_S11_L001_R1_001.fastq.gz RNA-Seq 508.4 MB
HM-OT-12_S12_L001_R1_001.fastq.gz RNA-Seq 563.3 MB
HM-OT-13_S13_L001_R1_001.fastq.gz RNA-Seq 724.0 MB
HM-OT-14_S14_L001_R1_001.fastq.gz RNA-Seq 568.2 MB
HM-OT-5_S5_L001_R1_001.fastq.gz RNA-Seq 663.2 MB
HM-OT-6_S6_L001_R1_001.fastq.gz RNA-Seq 681.5 MB
HM-OT-7_S7_L001_R1_001.fastq.gz RNA-Seq 632.3 MB
HM-OT-8_S8_L001_R1_001.fastq.gz RNA-Seq 544.0 MB
HM-OT-9_S9_L001_R1_001.fastq.gz RNA-Seq 715.2 MB
GSE232513 GSE · via ncbi_elink
GEO ↗

Expanded repertoire of RNA-editing-based detection for RNA binding protein interactions (1)

Homo sapiens

10 data files
FileTypeSize
D10_S18_L001_R1_001.fastq.gz RNA-Seq 273.6 MB
D11_S19_L001_R1_001.fastq.gz RNA-Seq 124.6 MB
D12_S20_L001_R1_001.fastq.gz RNA-Seq 406.1 MB
D2_S12_L001_R1_001.fastq.gz RNA-Seq 270.0 MB
D3_S13_L001_R1_001.fastq.gz RNA-Seq 243.5 MB
D4_S14_L001_R1_001.fastq.gz RNA-Seq 314.6 MB
D5_S15_L001_R1_001.fastq.gz RNA-Seq 269.5 MB
D8_S16_L001_R1_001.fastq.gz RNA-Seq 280.6 MB
D9_S17_L001_R1_001.fastq.gz RNA-Seq 235.0 MB
H1_S21_L001_R1_001.fastq.gz RNA-Seq 300.6 MB
GSE232518 GSE · via ncbi_elink
GEO ↗

Expanded repertoire of RNA-editing-based detection for RNA binding protein interactions (4)

Homo sapiens

10 data files
FileTypeSize
Torin_RS_01_S1_L004_R1_001.fastq.gz RNA-Seq 2.0 GB
Torin_RS_02_S2_L004_R1_001.fastq.gz RNA-Seq 4.8 GB
Torin_RS_03_S3_L004_R1_001.fastq.gz RNA-Seq 3.4 GB
Torin_RS_04_S4_L004_R1_001.fastq.gz RNA-Seq 4.2 GB
Torin_RS_05_S5_L004_R1_001.fastq.gz RNA-Seq 3.9 GB
Torin_RS_06_S6_L004_R1_001.fastq.gz RNA-Seq 2.9 GB
Torin_RS_09_S9_L004_R1_001.fastq.gz RNA-Seq 2.9 GB
Torin_RS_10_S10_L004_R1_001.fastq.gz RNA-Seq 4.2 GB
Torin_RS_11_S11_L004_R1_001.fastq.gz RNA-Seq 3.1 GB
Torin_RS_12_S12_L004_R1_001.fastq.gz RNA-Seq 4.5 GB
GSE232519 GSE · via ncbi_elink
GEO ↗

Expanded repertoire of RNA-editing-based detection for RNA binding protein interactions (5)

Homo sapiens

10 data files
FileTypeSize
15_S15_L001_R1_001.fastq.gz RNA-Seq 12.8 MB
16_S16_L001_R1_001.fastq.gz RNA-Seq 13.9 MB
17_S17_L001_R1_001.fastq.gz RNA-Seq 12.4 MB
18_S18_L001_R1_001.fastq.gz RNA-Seq 9.8 MB
19_S19_L001_R1_001.fastq.gz RNA-Seq 14.2 MB
20_S20_L001_R1_001.fastq.gz RNA-Seq 14.9 MB
21_S21_L001_R1_001.fastq.gz RNA-Seq 8.8 MB
22_S22_L001_R1_001.fastq.gz RNA-Seq 7.9 MB
23_S23_L001_R1_001.fastq.gz RNA-Seq 11.1 MB
24_S24_L001_R1_001.fastq.gz RNA-Seq 9.7 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
GSE215252 GSE · GEO GEO ↗ FLARE: A fast and flexible peak-calling pipeline for identifying RNA editing foci
Funding 12 grants
Grant Funder
U24 HG009889 NHGRI NIH HHS (United States)
R01 HG004659 NHGRI NIH HHS (United States)
U24 HG011735 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 NS103172 NINDS NIH HHS (United States)
U41 HG009889 NHGRI NIH HHS (United States)
K12 GM068524 NIGMS NIH HHS (United States)
R35 GM138317 NIGMS NIH HHS (United States)
T32 GM112584 NIGMS NIH HHS (United States)
R01 HG010646 NHGRI NIH HHS (United States)