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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression

ABSTRACT: The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression

PROVIDER: PRJNA436167 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6788180_1.fastq.gz	Fastqsanger.gz
	SRR6788180_2.fastq.gz	Fastqsanger.gz
	SRR6788690_1.fastq.gz	Fastqsanger.gz
	SRR6788690_2.fastq.gz	Fastqsanger.gz
	SRR6788181_1.fastq.gz	Fastqsanger.gz

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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 KO]

Project description:The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 KO]

| PRJNA436147 | ENA

The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 rescue]

Project description:The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 rescue]

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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 rescue]

Project description:To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship.

2018-04-25 | GSE111210 | GEO

The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression [ELL2 KO]

2018-04-25 | GSE111199 | GEO

The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression.

Project description:Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined?=?2.5?×?10-27; ?combined?=?-0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Our results provide mechanistic insight into MM predisposition.

| S-EPMC5917026 | biostudies-literature

The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-04-25 | GSE111211 | GEO

F1 allele specific gene expression

Project description:By comparing mouse fibroblasts from two parental strains (Bl6 and Spretus) with fibroblasts from their first generation offspring (F1) we can detect allele specific expression of proteins. The Bl6 and Spretus lines are evolutionary distant and harbour many SNPs in their genomes which when synonomous we can detect on the protein level using mass spectrometry. By mixing SILAC labeled Bl6, Spretus and F1 offspring cell lines we can detect peptides shared between all three cell lines and also SNP peptides that are only expressed in the F1 cells and either Bl6 or Spretus cells. By comparing the abundance of the shared peptides and the SNP peptides we can quantify how much of a protein in the F1 cells that comes from the paternal or maternal allele. This data were then further compared to polysome profiling data. Azidohomoalanine labeling was used to enrich newly synthesized proteins from the three cell lines.

2015-08-18 | PXD002337 | Pride

A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis

Project description:A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis

| PRJNA1072980 | ENA

Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

Project description:Ribosomes are often seen as monolithic machines produced from uniformly regulated genes. However, in yeast most ribosomal proteins come from duplicated genes. Here, we demonstrate that gene duplication may serve as an adaption mechanism modulating the global proteome through the differential expression of ribosomal proteins paralogs after exposure to stress. Our data indicate that the yeast paralog pair of the ribosomal protein L7/uL30 produces two differentially acetylated proteins. Under normal conditions most ribosomes incorporate the hypo-acetylated major form favoring the translation of genes with short open reading frames. Exposure to drugs, on the other hand, increases the production of ribosomes carrying the hyper-acetylated minor paralog that increases translation of long reading frames. Many of these long genes encode cell wall proteins that increase drug resistance in a programed change in translation equilibrium. Together the data reveal a mechanism of translation control through the differential fates of near-identical ribosomal protein isoforms.

2022-08-09 | GSE202803 | GEO

Ribosomal Proteins Regulate MHC Class I Peptide Generation for Immunosurveillance

Project description:The MHC class I antigen presentation system enables T cell immunosurveillance of cancers and viruses. Rapidly degraded nascent polypeptides (DRiPs) provide many class I peptide ligands. By knocking down each of the 80 ribosomal proteins, we identified proteins that modulate peptide generation without altering source protein expression. We show that 60S ribosomal proteins L6 (RPL6) and RPL28, which are adjacent on the ribosome, play opposite roles in generating an influenza A virus encoded peptide. RPL6 depletion decreases ubiquitin-dependent peptide presentation, while RPL28 depletion increases ubiquitin-dependent and -independent peptide presentation. 40S ribosomal protein S28 (RPS28) knockdown increases total peptide supply in uninfected cells by increasing DRiP synthesis from non-canonical translation of “untranslated” regions and non-AUG start codons, and sensitizes tumor cells for T cell targeting. RPL23 knocKDut decreases overall peptide supply, impairing T cell recognition of tumor cells. Our findings raise the possibility of modulating immunosurveillance by pharmacologically targeting ribosomes.

2019-01-21 | GSE114484 | GEO

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