GEO DataSets

(Submitter supplied) The fidelity of start codon recognition by ribosomes is paramount during protein synthesis. The textbook knowledge of eukaryotic translation initiation depicts 5’→3’ unidirectional migration of the pre-initiation complex (PIC) along the 5’UTR. In probing translation initiation from ultra-short 5’UTR, we report that an AUG triplet near the 5’ end can be selected via PIC backsliding. The bi-directional ribosome scanning is supported by competitive selection of closely spaced AUG codons and recognition of two initiation sites flanking an internal ribosome entry site. more...

Organism:

Homo sapiens; Mus musculus

Type:

Other

Platforms:

GPL17021 GPL18573 GPL19057

22 Samples

Download data: TXT

(Submitter supplied) Snapshot of translation in mammalian cells that are depleted of polyamines or replete with polyamines. Hek293T cells treated with DFMO or Spermidine.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL16791

4 Samples

Download data: CSV

(Submitter supplied) Translation is initiated by binding of the eIF4F complex to the 5' cap of the mRNA, which is followed by scanning of the initiation codon by scanning ribosomes. Here we demonstrate that the ASC-1 complex (ASCC), which was previously shown to promote the dissociation of colliding 80S ribosomes, associates with the scanning ribosomes to regulate translation initiation. Sel-TCP-seq analysis revealed that ASCC3, a subunit of ASCC with a helicase domain, localizes predominantly to the 5' untranslated region of mRNAs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24676

74 Samples

Download data: CSV

(Submitter supplied) The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in favorable context. Previous findings suggest that the factor eIF1 discriminates against non-AUG start codons by impeding full accommodation of Met-tRNAi in the P site of the 40S ribosomal subunit, necessitating eIF1 dissociation for start codon selection. Consistent with this, yeast eIF1 substitutions that weaken its binding to the PIC increase initiation at UUG codons on a mutant his4 mRNA and particular synthetic mRNA reporters; and also at the AUG start codon of the mRNA for eIF1 itself owing to its poor Kozak context. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17342

4 Samples

Download data: WIG

(Submitter supplied) DEAD-box RNA helicases eIF4A and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. eIF4B is a cofactor for eIF4A but might also function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17342

16 Samples

Download data: CSV

(Submitter supplied) Aberrant translation initiation at non-AUG start codons is associated with multiple cancers and neurodegenerative diseases. Nevertheless, how non-AUG translation is regulated differently from canonical translation is poorly understood. We thus used start codon-selective  reporters and ribosome profiling to characterize how translation from non-AUG start codons responds to protein synthesis inhibitors in human cells. more...

Organism:

Homo sapiens

Type:

Other; Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: CSV, TSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Other; Expression profiling by high throughput sequencing

Platform:

GPL18573

28 Samples

Download data

(Submitter supplied) Sequences within 5' untranslated regions (UTRs) dictate the site and efficiency of translation initiation. In this study, an unbiased screen designed to interrogate the 5' UTR-mediated regulation of the growth-promoting gene MYC unexpectedly revealed the ribosomal pause-relief factor eIF5A as a regulator of translation initiation codon selection. Depletion of eIF5A enhanced upstream translation within 5' UTRs across yeast and human transcriptomes, including on the MYC transcript where this resulted in increased production of an N-terminally extended protein. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL18573

16 Samples

Download data: TXT

(Submitter supplied) Sequences within 5' untranslated regions (UTRs) dictate the site and efficiency of translation initiation. In this study, an unbiased screen designed to interrogate the 5' UTR-mediated regulation of the growth-promoting gene MYC unexpectedly revealed the ribosomal pause-relief factor eIF5A as a regulator of translation initiation codon selection. Depletion of eIF5A enhanced upstream translation within 5' UTRs across yeast and human transcriptomes, including on the MYC transcript where this resulted in increased production of an N-terminally extended protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: XLSX

(Submitter supplied) Sequences within 5' untranslated regions (UTRs) dictate the site and efficiency of translation initiation. In this study, an unbiased screen designed to interrogate the 5' UTR-mediated regulation of the growth-promoting gene MYC unexpectedly revealed the ribosomal pause-relief factor eIF5A as a regulator of translation initiation codon selection. Depletion of eIF5A enhanced upstream translation within 5' UTRs across yeast and human transcriptomes, including on the MYC transcript where this resulted in increased production of an N-terminally extended protein. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL18573

6 Samples

Download data: XLSX

(Submitter supplied) Most animal mRNAs contain upstream Open Reading Frames (uORFs). These uORFs represent an impediment to translation of the main ORF since ribosomes usually bind the mRNA cap at the 5’ end and then scan for ORFs in a 5’-to-3’ fashion. One way for ribosomes to bypass uORFs is via leaky scanning, whereby the ribosome disregards the uORF start codon. Hence leaky scanning is an important post-transcriptional mechanism affecting gene expression. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL21697

16 Samples

Download data: XLSX

(Submitter supplied) Translation regulation occurs largely during initiation. Currently, translation initiation can be studied in vitro, but these systems lack features present in vivo and on endogenous mRNAs. Here we develop selective 40S footprinting for visualizing initiating 40S ribosomes on endogenous mRNAs in vivo. It pinpoints where on an mRNA initiation factors join the ribosome to act, and where they leave. We discover that in human cells most scanning ribosomes remain attached to the 5’ cap. more...

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL21697 GPL21626

60 Samples

Download data: XLSX

(Submitter supplied) The Ribo-seq analysis demonstrated that eIF1A is predominantly essential for translation of genes with long 5'UTR genes including cell proliferation and cell cycle progression genes. eIF1A depletion causes broad stimulation of initiation in 5’UTRs at near-cognate AUG codons that diminshes the translation initiation fidelity

Organism:

Mus musculus

Type:

Other

Platform:

GPL17021

4 Samples

Download data: TXT

(Submitter supplied) The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian ortholog DDX3 are critical for translation initiation. Mutations in DDX3 are linked to tumorigenesis and intellectual disability, and the enzyme is targeted by diverse viruses. How Ded1p and its orthologs engage RNAs to impact translation initiation has been a longstanding, unresolved question. Here we show that Ded1p associates with the pre-initiation complex at the mRNA entry channel of the small ribosomal subunit and that the helicase unwinds mRNA structure ahead of the scanning pre-initiation complex. more...

Organism:

Saccharomyces cerevisiae

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL21656 GPL17342

38 Samples

Download data: TAB, TXT

(Submitter supplied) We have developed a deep sequencing-based approach, Rec-Seq, that allows simultaneous monitoring of ribosomal 48S pre-initiation complex (PIC) formation on every mRNA in the translatome in an in vitro reconstituted system. Rec-Seq isolates key early steps in translation initiation in the absence of all other cellular components and processes. Using this approach we show that the DEAD-box ATPase Ded1 promotes 48S PIC formation on the start codons of >1000 native mRNAs, most of which have long, structured 5’-untranslated regions (5’UTRs). more...

Organism:

Saccharomyces cerevisiae

Type:

Other

Platform:

GPL27812

14 Samples

Download data: WIG

(Submitter supplied) Rocaglamide A (RocA) typifies a class of protein synthesis inhibitors that selectively kill aneuploid tumor cells and repress translation of specific mRNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase; its mRNA selectivity is proposed to reflect highly structured 5′ UTRs that depend strongly on eIF4A-mediated unwinding. However, rocaglate treatment may not phenocopy the loss of eIF4A activity, as these drugs actually increase the affinity between eIF4A and RNA. more...

Organism:

synthetic construct; Homo sapiens

Type:

Other

Platforms:

GPL21616 GPL20301

8 Samples

Download data: FA

(Submitter supplied) Rocaglamide A (RocA) typifies a novel class of protein synthesis inhibitors that selectively kill aneuploid tumor cells and repress translation of specific mRNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), the prototypical DEAD-box RNA helicase, and its mRNA selectivity is proposed to reflect highly structured 5′ UTRs that are very dependent on eIF4A-mediated unwinding. Here, we show that secondary structure in 5′ UTRs is only a minor determinant for RocA selectivity and RocA does not repress translation by reducing eIF4A activity. more...

Organism:

synthetic construct; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL11154 GPL15228

23 Samples

Download data: FA, TXT

(Submitter supplied) Translation start site selection in eukaryotes is influenced by context nucleotides flanking the AUG codon and by levels of the eukaryotic translation initiation factors eIF1 and eIF5. In a search of human genes, we identified 5 Hox gene paralogs initiated by AUG codons in conserved suboptimal context as well as 13 Hox genes that contain evolutionarily conserved upstream open reading frames (uORFs) that initiate at AUG codons in poor sequence context. more...

Organism:

Mus musculus

Type:

Other

Platform:

GPL17021

3 Samples

Download data: WIG

(Submitter supplied) The integrated stress response (ISR) facilitates cellular adaptation to a variety of stress conditions via phosphorylation of the common target eIF2α. During ISR, the translation of certain stress-related mRNAs is upregulated in spite of global suppression of protein synthesis.The selective translation often relieson alternative mechanisms, such as leaky scanning or reinitiation, but the underlying mechanism remains incompletely understood. more...

Organism:

Mus musculus

Type:

Other; Expression profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing

Platform:

GPL9185

29 Samples

Download data: TXT

(Submitter supplied) Cellular stress is often accompanied by non-canonical initiation of translation at alternate start codons in mammalian cells. Here we systematically investigate the extent and impact of alternate translation initiation in the context of influenza virus infection. We use ribosome profiling with the initiation inhibitor lactidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL16791

12 Samples

Download data: TSV, TXT