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Transcriptome-wide identification of RNA-binding protein binding sites using seCLIP-seq.

Nature protocols · 2022 · Vol. 17 (5) · pp. 1223-1265

Abstract

Discovery of interaction sites between RNA-binding proteins (RBPs) and their RNA targets plays a critical role in enabling our understanding of how these RBPs control RNA processing and regulation. Cross-linking and immunoprecipitation (CLIP) provides a generalizable, transcriptome-wide method by which RBP/RNA complexes are purified and sequenced to identify sites of intermolecular contact. By simplifying technical challenges in prior CLIP methods and incorporating the generation of and quantitative comparison against size-matched input controls, the single-end enhanced CLIP (seCLIP) protocol allows for the profiling of these interactions with high resolution, efficiency and scalability. Here, we present a step-by-step guide to the seCLIP method, detailing critical steps and offering insights regarding troubleshooting and expected results while carrying out the ~4-d protocol. Furthermore, we describe a comprehensive bioinformatics pipeline that offers users the tools necessary to process two replicate datasets and identify reproducible and significant peaks for an RBP of interest in ~2 d.

Publication Types

["Journal Article", "Review", "Research Support, N.I.H., Extramural"]

Keywords

[]

MeSH Terms

["Binding Sites", "High-Throughput Nucleotide Sequencing", "Immunoprecipitation", "Protein Binding", "RNA", "RNA-Binding Proteins", "Transcriptome"]

Funding

U24 HG009889 NHGRI NIH HHS (United States)
R01 HG004659 NHGRI NIH HHS (United States)
R00 HG009530 NHGRI NIH HHS (United States)
U41 HG009889 NHGRI NIH HHS (United States)
K99 HG009530 NHGRI NIH HHS (United States)

Linked Datasets (1)

GSE180686 GSE via ncbi_elink
GEO

Transcriptome-wide identification of RNA binding protein binding sites using seCLIP-seq

Homo sapiens
5 data files
FileTypeSize
4114_CLIP1_S39_L002_R1_001.fastq.gz RIP-Seq 684.8 MB
4114_CLIP2_S41_L002_R1_001.fastq.gz RIP-Seq 645.2 MB
4114_INPUT1_S38_L002_R1_001.fastq.gz RIP-Seq 655.7 MB
4114_INPUT2_S40_L002_R1_001.fastq.gz RIP-Seq 629.8 MB
SRR15222630.lite RIP-Seq 629.8 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.

ENCFF159KBI ENCFF ENCODE

Analysis Pipelines (1)

eCLIP geo_data_processing GSE180686