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SRX1801618: GSM2177899: 6A_RP; Saccharomyces cerevisiae; OTHER
1 ILLUMINA (Illumina HiSeq 2500) run: 11.9M spots, 595.2M bases, 325.1Mb downloads

Submitted by: NCBI (GEO)
Study: Ribosome profiling of synchronous, non-arrested yeast cells identifies translational control of lipid biosynthesis enzymes in the cell cycle
show Abstracthide Abstract
The translational efficiency of mRNAs in cells progressing synchronously through the mitotic cell cycle and having to meet their growth requirements for cell division has not been interrogated. Here, we used ribosome profiling of a cell-size series from the time of cell birth, to identify for the first time yeast mRNAs under periodic translational control. Late in the cell cycle, there was coordinate translational activation of mRNAs encoding lipid biosynthesis enzymes. An upstream open reading frame (uORF) mediates the translational control of ACC1, the mRNA encoding the rate-limiting enzyme acetyl-CoA carboxylase. The ACC1 uORF also adjusts Acc1p protein levels in different nutrients. Mutating the ACC1 uORF delayed cell cycle progression, reduced cell size and suppressed the replicative longevity of cells lacking the Sch9p protein kinase, the yeast S6 kinase ortholog. These findings reveal unexpected links between lipogenesis and protein synthesis in mitotic cell divisions Overall design: We used centrifugal elutriation to isolate growing, highly synchronous, unbudded, early G1 cell populations and scored the elutriated cultures over time microscopically, recording the percentage of budded cells with a particle counter that directly measures their volume (channelyzer). Generation of both the Ribosome Profile (RP) and Transcriptional Profile (TP) libraries require at least =2E+09 yeast cells per sample. Such sample size could not be collected following a typical time-series experiment because only a small minority of the total cell population is in early G1 at any given moment. Instead, we allowed the entire cell population of each elutriated fraction to progress in the cell cycle until it reached a given cell size (e.g., 40 fl), at which point the sample was harvested. Elutriated cells of the same size were pooled together until enough cells per sample were obtained. This pool of same-size cells defined one experimental replicate (e.g., Sample01A). We harvested cells with 5fl cell size increments, from the time they are born (40 fl -- Sample01), until the end of the cell cycle (75 fl -- Sample08). In total we generated three independent Experimental Replicates for each cell size (A, B and C). We have: Sample01A, 01B and 01C (40 fl); Sample02A, 02B and 02C (45 fl), Sample03A, 03B and 03C (50 fl), Sample04A, 04B and 04C (55 fl), Sample05A, 05B and 05C (60 fl), Sample06A, 06B and 06C (65 fl), Sample07A, 07B and 07C (70 fl) and Sample08A, 08B and 08C (75 fl). Samples are divided into two series: Ribosome Profile (RP) and Transcriptional Profile (TP).
Sample: 6A_RP
SAMN05179469 • SRS1468313 • All experiments • All runs
Library:
Instrument: Illumina HiSeq 2500
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: SINGLE
Construction protocol: For the mRNA libraries, cells were lysed and total RNA isolated using the RNeasy kit (Qiagen, Cat#: 74104), which was then used to isolate poly(A)+ RNA with the Oligotex kit (Qiagen, Cat#: 70022). The purified mRNA from each sample was then used with the ScriptSeq v2 RNA-Seq library preparation kit (Illumina, Cat#: SSV21124), exactly according to the manufacturer’s instructions. In the final PCR amplification of the libraries, the forward primer was the one included in the ScriptSeq v2 RNA-Seq kit, while the reverse index PCR primers used for the mRNA libraries were primers 1 through 8, from the ScriptSeq Set 1 (Illumina, Cat#: RSBC10948) For the ribosome footprint libraries, the cell extracts were prepared as follows: The cell pellets were in 1.5 ml screw-cap microcentrifuge tubes and they were washed once with 1 ml ice-cold DEPC-treated water, centrifuged at 13,000 g for 1 min and the supernatant was aspirated. To each tube we added 0.25 ml glass beads (425-600 μm; Sigma-Aldrich, Cat#: G9268) and 0.4 ml ice-cold lysis buffer, which is described in Ingolia et al(Ingolia et al., 2012). The cells were broken by vortexing at full speed eight times, for 15 sec each time. The samples were placed in ice for at least 30 sec between each vortexing. The extracts were clarified by centrifugation at 5,000 g for 5 min, at 4 °C. The supernatant was clarified in a second centrifugation, at 13,000 g for 10 min, at 4 °C. All subsequent steps for the ribosome footprint libraries were performed as described in Ingolia et al(Ingolia et al., 2012), except step 7, where we used 1.875 μl of RNase I (100 U μl-1) per reaction. For all gel extractions, we used the overnight protocol described in(Ingolia et al., 2012). Depletion of rRNA was done as described in (Ingolia et al., 2012). In the final PCR amplification and barcode addition step, we amplified each library for 12 cycles
Experiment attributes:
GEO Accession: GSM2177899
Links:
Runs: 1 run, 11.9M spots, 595.2M bases, 325.1Mb
Run# of Spots# of BasesSizePublished
SRR359074211,903,802595.2M325.1Mb2017-01-11

ID:
2577179

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