Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Analysis of Kozak sequences variants of haploinsufficient genes

ABSTRACT: Analysis of Kozak sequences variants of haploinsufficient genes

PROVIDER: PRJNA863493 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR20707616.fastq.gz	Fastqsanger.gz
	SRR20707617.fastq.gz	Fastqsanger.gz
	SRR20707618.fastq.gz	Fastqsanger.gz
	SRR20707619.fastq.gz	Fastqsanger.gz
	SRR20707620.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Analysis of Kozak sequences variants of haploinsufficient genes

Project description:We conceived that the availability of base editors and the possible presence of suboptimal Kozak sequences in the human genome could provide an elegant approach to modulate translational efficiency for the molecular compensation of some haploinsufficient disorders. Moreover, such an approach would be independent of the type of alteration inactivating the defective allele and, therefore, highly suitable for gene therapy protocols. To find base conversions upregulating translational efficiency, we systematically screened 5261 (4621 unique) variants of Kozak sequences for translational strength. We designed these variants in the main AUG context of 230 previously annotated haploinsufficient genes. Analysis of our library of Kozak variants, bearing the conversions that base editors can reproduce, proved that weak Kozak sequences are present at about a 20% frequency in our gene sample. We validated the variants of five genes and base edited one of them in a cell model, providing proof of principle of the approach, which we called BOOST (Base editing cOrrection of haplOinSufficiency by Translational enhancement).

2022-09-13 | GSE210035 | GEO

Kozak sequence libraries for characterizing transgenes across expression levels

Project description:Typical mammalian overexpression systems test protein sequence variants with little control over expression levels and steady-state protein abundances, hindering interpretations of how protein sequence and expression converge to yield phenotypic outcomes. We explored the translation initiation sequence, commonly referred to as the Kozak sequence, as a means to modulate protein steady-state abundance and cellular function. We performed sort-seq on a randomized library of the 6 nucleotides preceding the start codon, amounting to 4,042 sequences. Calibrating the scores revealed a ~100-fold range of protein steady-state abundances possible through manipulation of the Kozak sequence. We identified human germline variants with predicted expression-reducing Kozak substitutions in disease-associated genes. Modulating the cell surface abundance of the host cell receptor ACE2 controlled the rate at which those cells became infected by SARS-like coronavirus spike pseudotyped particles. We demonstrated the potential of the approach by simultaneously testing Kozak libraries with a small panel of coding variants for ACE2 and STIM1. This approach lays the methodological groundwork for linking the causal relationships between protein sequence, abundance, and functional outcome.

2025-05-01 | GSE295498 | GEO

HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis

Project description:Photosynthesis requires chloroplasts, where most proteins are nucleus-encoded and produced via cytoplasmic translation. The translation initiation factor eIF5B gates the transition from initiation (I) to elongation (E), and the Kozak motif is associated with translation efficiency, but their relationship is previously unknown. Here, with ribosome profiling, we determined the genome-wide I-E transition efficiencies. We discovered that the most prevalent Kozak motif is associated with high I-E transition efficiency in Arabidopsis, rice, and wheat, thus implicating the Kozak motif in facilitating the I-E transition. Indeed, the effects of most Kozak motifs, including the most effective ones, depend on HOT3/eIF5B1 in Arabidopsis. HOT3 preferentially promotes the translation of photosynthesis-associated nuclear genes in a Kozak motif-dependent manner, which explains the chloroplast defects of hot3 mutants. Our study reveals an evolutionarily-conserved link between the Kozak motif and eIF5B-mediated translational I-E efficiency and elucidates a HOT3-mediated translational control of nuclear photosynthesis genes for chloroplast biogenesis.

2024-10-03 | GSE212856 | GEO

HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis

2024-10-03 | GSE212855 | GEO

959 Sequences of bHLH genes

Project description:CDS Sequences of bHLH genes

| PRJEB36432 | ENA

Regulatory variants of blood pressure genes

Project description:Regulatory variants of blood pressure genes

| PRJNA881331 | ENA

Patogenic Mutation in 5 Genes

Project description:This is a pathogenic mutation profile of colorectal patients specifically in 5 genes, i.e. APC, TP53, PIK3CA, KRAS, and MLH1. Single nucleotide variants identified were synchronized with patients’ characteristics.

| 2384421 | ecrin-mdr-crc

Rps26 directs mRNA-specific translation by recognition of Kozak sequence elements

Project description:The “Kozak sequence”, immediately upstream of the start codon, regulates the translational efficiency of an mRNA. Nevertheless, how this sequence is recognized remains unexplored. Here, we describe a novel approach to separate two ribosome populations from the same cells and use this method, and RNA-seq, to identify the mRNAs bound to ribosomes with and without Rps26, a protein linked to the pathogenesis of Diamond Blackfan Anemia (DBA). These analyses reveal that Rps26 contributes to recognition of the Kozak sequence in well-translated mRNAs, and that Rps26-deficient ribosomes preferentially translate mRNA from select stress response pathways. Surprisingly, we demonstrate that exposure of cells to these stresses leads to the formation of Rps26-deficient ribosomes and to the translation of their targets. Thus, Rps26-deficient ribosomes play aberrant pathogenic roles in DBA as well as physiological roles in augmenting the well-characterized stress transcriptional response with a heretofore unknown translational stress response, thereby creating a feed forward loop in gene-expression.

2017-07-30 | GSE86203 | GEO

HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis

Project description:HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis

| PRJNA877650 | ENA

HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis

Project description:HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis

| PRJNA877653 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data