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SRX17444176: GSM6547491: HNRNPD_3FHBH_IP; Homo sapiens; OTHER
1 ILLUMINA (Illumina NovaSeq 6000) run: 68.4M spots, 3.4G bases, 1.1Gb downloads

External Id: GSM6547491_r1
Submitted by: School of Life Sciences, University of Science and Technology of China
Study: High-throughput sequencing in HNRNPD knock-out and knock-in HEK293T cell lines
show Abstracthide Abstract
As HNRNPD regulates the alternative splicing of hundreds of genes, we sought to investigate whether HNRNPD could regulate the biogenesis of circRNAs. To identify the effect of HNRNPD on circRNAs and linear RNAs, we performed circRNA and linear RNAs (ployA enrichment RNA and lncRNA) sequencing in HNRNPD knockout and wild-type HEK293T cells. We also inserted 3FHBH (3xFLAG, Histidine, Biotin, and Histidine) into the HNRNPD genome to obtain HEK293T_HNRNPD_3FHBH cells by using CRISPR-Cas9 technology, which was used to ascertain the direct HNRNPD targeting RNA sequence with the help of FLASH sequencing (Fast Ligation of RNA after some sort of Affinity Purification for High-throughput Sequencing). To evaluate the impacts of HNRNPD deficiency on circRNA formation, we captured nascent RNA in HEK293T and HNRNPD knock-out HEK293T cells by immunoprecipitation of 5-ethyluridine (EU) labeling. Comparative analysis of these data, we found the higher propensity of binding to introns of HNRNPD was related to inhibiting circRNA biogenesis. Overall design: We used CRISPR-Cas9 technology to generate HNRNPD knock-out and knock-in HEK293T cell lines. We extracted total RNA and digested it with RNase R in HNRNPD knock-out and wild-type HEK293T cell lines for circRNA sequencing; In the HEK293T_HNRNPD_3FHBH cell, we followed the entire FLASH protocol to collect the RNA that was bound by HNRNPD. Next, the RNA was performed for FLASH sequencing; Culturing to 80% confluence, the cell transcription was terminated with 5,6-dichloro-1-ß-D- ribofuranosylbenzimidazole (DRB, final concentration 0.5 mM) for 3 hours in HNRNPD knock-out and wild-type HEK293T cell lines. Subsequently, the culture media was changed with fresh DMEM medium adding 5-ethyluridine (EU, final concentration 0.25 mM) for another 1 hour. Then the nascent RNA was immunoprecipitated with streptavidin-conjugated magnetic beads and extracted with Trizol reagent. The nascent RNAs were to conduct RIP-sequencing.
Sample: HNRNPD_3FHBH_IP
SAMN30686105 • SRS14998215 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM6547491
Instrument: Illumina NovaSeq 6000
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: SINGLE
Construction protocol: For circRNA-sequencing, RNA was extracted with Trizol. For FLASH-sequencing, the HEK293T_HNRNPD_3FHBH cells were crosslinked by UV irradiation. After a series of operations (harvested, lysed, sonicated, and immunoprecipitated), the cells were fixed with 90% ethanol and linked up with azide-labeled biotin in the click reaction solution (DPBS, 2.5 mM biotin-azide, 3 mM CuSO4, 6 mM Tris(3-hydroxypropyltriazolymethyl) amine, 10 mM aminoguanidine and 50 mM sodium L-ascorbate). Then the cells were washed with DPBS (containing 0.5% Triton X-100 and 2 mM EDTA) and DPBS. Discarding the DPBS, the cells were transferred into a 1.5 ml tube and suspended with lysis buffer (20 mM Tris-Cl (pH 7.5), 500 mM LiCl, 1 mM EDTA, 0.5% lithium-dodecylsulfate, 5 mM DTT, and 0.1 U/µl RNase inhibitor) on the ice and homogenized through a syringe with a 0.4 mm diameter-needle 5 times. The nascent RNAs were immunoprecipitated with streptavidin-conjugated magnetic beads. Finally, the magnetic beads were washed with washing buffer and isolated from magnetic beads by RNA elution buffer (10 mM EDTA (pH 8.2) and 95% formamide), and digested with proteinase K. The nascent RNAs were extracted with Trizol reagent. For circRNA detection, samples were digested by RNase R to remove linear transcripts after ribosomal RNA (rRNA) depletion. Strand-specific libraries (also known as stranded/directional libraries) were prepared. For FLASH-sequencing, the immunoprecipitated RNA-HNRNPD complex was digested by RNaseI and TURBO DNase, followed by dephosphorylation. The complex was ligated with an s-oligo using T4 RNA ligase I, which was also followed by dephosphorylation. The complex was resuspended with proteinase K digestion buffer to release crosslinked RNA, and column purification (Zymo DNA Clean and Concentrator). The purified RNA was executed reverse transcription with SuperScript III, and column purification. The cDNA was then circularized with CircLigase. The cyclized cDNA was the template of PCR reaction with NEBNext High-Fidelity Master Mix. Then the PCR products were cleaned up with l.5 X AM pure beads. For RIP-sequencing, the Illumina Ribo-Zero Gold kit removed rRNA, and surplus RNA was purified for end repair and 50-adaptor ligation. Reverse transcription was performed with random primers containing 3' adaptor sequences. Finally, the cDNAs were purified and amplified with PCR reactions. The products with lengths of 300-500 were purified and quantified. These libraries were utilized for 150 nt paired-end sequencing with an Illumina Nova seq 6000 system (Novogene, China).
Runs: 1 run, 68.4M spots, 3.4G bases, 1.1Gb
Run# of Spots# of BasesSizePublished
SRR2144022468,357,5103.4G1.1Gb2023-09-30

ID:
24274818

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