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SRX8537874: GSM4613694: BY4741_DSN_rep2; Saccharomyces cerevisiae; OTHER
1 ILLUMINA (NextSeq 500) run: 8M spots, 597M bases, 223.9Mb downloads

Submitted by: NCBI (GEO)
Study: Development of High-throughput 5Pseq and detection of ribosome stalls at termination level in Saccharomyces cerevisiae
show Abstracthide Abstract
We developed a high throughput 5'P sequencing approach (HT-5PSeq) to investigate 5'P mRNA degradome in relation with translation process. This approach is easy and scalable; and uses an affordable rRNA depletion based on duplex-specific nuclease treatment. We use it to investigate in vivo ribosome stalls in S. cerevisiae and S. pombe at single nucleotide resolution. We investigate the 5'P degradation profiles associated to ribosome pausing, its regulation in stress conditions and the relative poly(A) length of mRNA degradation intermediates. Overall design: We performed 2 biologically independent HT-5PSeq experiments. For S.cerevisiae, we performed HT-5Pseq with DSN treatment with probes targeting ribosomal rRNA (BY-DSN) and none DSN treatment (BY-NonDSN) , DSN treatment without probes (BY-NP) as control. We also performed 5Pseq (PMID: 26046441) in S.cerevisiae as positive control. For S.pombe, we performed HT-5Pseq with DSN treatment with probes (orginally designed for S.cerevisiae ribosomal rRNA) (Pombe-DSN) and none DSN treatment (Pombe-NonDSN) as control.To inhibit translation process, we used cycloheximide (CHX) as a translation inhibitor on S.cerevisiae (BY-CHX) and S.pombe (Pombe-CHX). In addition, we performed HT-5Pseq under different growth conditions. For early exponential phase, strains were grown to a final OD600 of 0.3 (BY-lowOD). To reach stationary stage, strains were grown during 60h in YPD (BY-Stationary). We performed paired-end sequencing for read1 (61bp) and read2 (15bp) in some samples (see below). We splited libraries with polyA and non-polyA based on the length of As in read2. For other samples, we performed single end sequencing.
Sample: BY4741_DSN_rep2
SAMN15223865 • SRS6832827 • All experiments • All runs
Library:
Instrument: NextSeq 500
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: PAIRED
Construction protocol: Total RNA was isolated by the standard phenol: chloroform method, and DNA was removed by DNase I treatment. The amount of RNA was quantified in a Nanodrop 2000 Spectrophotometer (Thermo Scientific) and RNA integrity was checked by agarose gel electrophoresis. For HT5Pseq libraries construction, we used 6 μg of DNA-free total RNA. Samples were directly subjected to RNA ligation. The treated RNA samples were incubated with 100 μM RNA/RNA rP5_RND oligo (final 10 μM) 2h at 25°C with 10 Units of T4 RNA ligase 1 (NEB). Ligated RNA was purified with RNAClean XP (Beckman Coulter), according to the manufacturer's instructions. RNA was reverse transcribed with Superscript II (Life Technologies) and primed with Illumina PE2 compatible oligos containing random hexamers (20 μM) and oligo-dT (0.05 μM). Reverse transcription reaction was incubated for 10 min at 25°C, 50 min at 42°C and heat inactivation for 15 min at 70°C. To deplete RNA in RNA/cDNA hybrid after reverse transcription, we used sodium hydroxide (40 mM) for incubation 20 min at 65°C and then neutralized with Tris-HCl, pH =7.0 (40 mM). For DSN (Duplex-specific nuclease) based rRNA depletion, we used a mixture of probes targeted the 18S rDNA, 25S rDNA and 5.8S rDNA. The probes were designed to occupy the whole ribosomal RNA regions with consecutive 25-30nt long unmodified DNA oligos. The hybridization of probes (2 μM each) with cDNAs were incubated at 68 °C for 2 minutes before adding pre-warmed DSN buffer mix with 1 Units of DSN enzyme (Evrogen). The reaction then performed at 68 °C for 20 minutes. To inactive DSN enzyme, we added 2X DSN stop solution and incubate 10 min at 68 °C. The final PCR amplification was used 2X Phusion High-Fidelity PCR Master Mix with HF Buffer (NEB) and final 0.1 μM of PE1.0 and corresponding multiplex PE2.0_MTX . The program followed this: 30s 98°C; 15 cycles (20s 98°C; 30s 65°C; 30s 72°C); 7min 72°C. Libraries were size selected using 0.7x-0.9x (v/v) AMpure XP beads (Beckman Coulter) to final 200-500 bp and sequenced by NextSeq 500/550 using 60 sequencing cycles for Read 1 and 15 cycles for Read 2. 5PSeq methods was performed as previously described (PMID: 26820793). 6µg of total RNA was used as input. In brief a RNA oligo (rP5_RND) containing an Illumina adaptor and unique molecular identifiers (UMI) was ligated to the intermediates of mRNA co-translation degradation (5'P). Ribosomal RNA was depleted using Ribo-Zero Magnetic Gold Kit (Illumina).Libraries were PCR amplified (15 cycles). Ampure beads size selected libraries with an average length of 451 nt were sent for sequencing (llumina NextSeq 500 instrument).
Experiment attributes:
GEO Accession: GSM4613694
Links:
Runs: 1 run, 8M spots, 597M bases, 223.9Mb
Run# of Spots# of BasesSizePublished
SRR120046847,975,072597M223.9Mb2021-04-04

ID:
11095413

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