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SRX668996: GSM1464237: Lib66PUCanAlbYPD2hr_input; Candida albicans; RNA-Seq
1 ILLUMINA (Illumina HiSeq 2500) run: 14.1M spots, 844.2M bases, 399.9Mb downloads

Submitted by: Gene Expression Omnibus (GEO)
Study: Transcriptome-wide mapping reveals widespread dynamic regulated pseudouridylation of mRNA
show Abstracthide Abstract
Pseudouridine is the most abundant modification occurring on RNA, yet with the exception of a few well-studied RNA molecules little is known about the modified positions and their function(s). Here, we develop ?-seq, a method for transcriptome-wide quantitative mapping of pseudouridine. We validate ?-seq with synthetic spike-ins and de novo identification of the vast majority of previously reported pseudouridylated positions. ?-seq permits discovery of hundreds of novel pseudouridine modifications in human and yeast mRNAs and snoRNAs. Knockdown and knockout of pseudouridine synthases uncovers the cognate PUSs mediating pseudouridine catalysis at these individual novel sites and their target sequence features. In both human and yeast pseudouridine formation on mRNA depends on both site-specific PUSs – often guided by a specific sequence motif - and snoRNA-guided PUSs. Importantly, upon heat shock in yeast, Pus7-mediated pseudouridylation is induced at >200 sites in diverse mRNAs. Pus7 deletion in yeast leads to decreased recovery from heat shock and decreased RNA levels at otherwise pseudouridylated messages, suggesting a role for pseudouridine in enhancing transcript stability. Pseudouridine stoichiometries in rRNA are highly conserved from yeast to mammals, but are reduced in cells derived from dyskeratosis congenita patients, where the pseudouridine synthase DKC1 is mutated, compared to age matched controls. Our results establish pseudouridine as a ubiquitous and dynamic modification in mRNA, and provide a sensitive, quantitative and transcriptome-wide methodology to address its underlying mechanisms and function. Overall design: Examination of m6A methylation in human Hek293 and A549 cell lines, in human embryonic stem cells (ESCs) undergoing differentiation to neural progenitor cells (NPCs), in OKMS inducible fibroblasts reprogrammed into iPSC, and upon knockdown of factors using siRNAs or shRNAs.
Sample: Lib66PUCanAlbYPD2hr_input
SAMN02951197 • SRS673286 • All experiments • All runs
Library:
Instrument: Illumina HiSeq 2500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Enrichment of polyadenylated RNA (polyA+ RNA) from total RNA was performed using one round of enrichment using Oligo(dT) dynabeads (Invitrogen) according to the manufacturer’s protocol. CMC-treatment was performed essentially as described in (Bakin and Ofengand, 1993; Bakin and Ofengand, 1998). Specifically, pelleted polyA+ RNA was resuspended in 30 mL of 0.17M CMC in BEU buffer (50mM bicine, pH 8.3, 4 mM EDTA, and 7M urea) or in 30 mL of BEU buffer as input at 37°C for 20 min. Reaction was stopped with 100 mL of 0.3M NaOAc and 0.1 mM EDTA, pH 5.6 (Buffer A), 700 mL of EtOH, and 1 mL of glycogen. After chilling for 5 min in dry ice, the pellet was recovered, washed with 70% EtOH, dissolved in 100 mL of Buffer A, and reprecipitated with 300 mL of EtOH and 1 mL of glycogen. After washing as above, the pellet was dried, dissolved in 40 mL of 50 mM sodium bicarbonate, pH 10.4, and incubated at 37°C for 3 hours. The RNA was precipitated by addition of 100 mL of Buffer A, 700 mL EtOH, and 1 mL of glycogen. The pellet was washed with 70 % EtOH and then dissolved with water for subsequent library preparation. The mRNA was chemically fragmented into ~80-150 nt-long fragments by performing a short fragmentation (30 seconds) using RNA fragmentation reagent and stop solution (Ambion). RNA was subjected to FastAP Thermosensitive Alkaline Phosphatase (Thermo Scientific), followed by a 3’ ligation of an RNA adapter using T4 ligase (New England Biolabs). Ligated RNA was reverse transcribed using AffinityScript Multiple Temperature Reverse Transcriptase (Agilent) or SuperScript III (Life Technologies), and the cDNA was subjected to a 3’ ligation with a second adapter using T4 ligase. The single-stranded cDNA product was then amplified for 9-12 cycles in a PCR reaction. Libraries were sequenced on Illumina HiSeq 2500 platforms generating paired end reads (30 bp from each end).
Experiment attributes:
GEO Accession: GSM1464237
Links:
External link:
Runs: 1 run, 14.1M spots, 844.2M bases, 399.9Mb
Run# of Spots# of BasesSizePublished
SRR153585514,070,540844.2M399.9Mb2014-09-15

ID:
937470

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