Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

ABSTRACT: 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 a stress-adaptation mechanism modulating the global proteome through the differential expression of ribosomal protein paralogs. 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 open reading frames. Many of these paralogs dependent genes encode cell wall proteins that could promote tolerance to drugs as their translation increases after exposure to drugs. Together the data reveal a mechanism of translation control through the differential use of near-identical ribosomal protein isoforms.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Mathieu Catala

LAB HEAD: Sherif Abou Elela

PROVIDER: PXD033843 | Pride | 2022-08-09

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	517Mathieu_L7_AA_LysC.raw	Raw
	517Mathieu_L7_BB_LysC.raw	Raw
	520Mathieu_2_AA_LysC.raw	Raw
	520Mathieu_2_BB_LysC.raw	Raw
	524Mathieu_MC1.raw	Raw

Items per page:

1 - 5 of 24

Similar Datasets

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

Specialized ribosomal protein genes promote drug resistance through modulation of translation

Project description:Ribosomes are ubiquitous ribonucleoprotein complexes required for protein synthesis. We show that in budding yeast exposure to drugs alters ribosome composition leading to modification of translation pattern and increased resistance to drug. Exposure to staurosporine repressed translation of cell wall protein genes. Expression of the major paralog of uL30/RPL7 increased cell sensitivity to staurosporine while expression of the minor paralog induced resistance. Remarkably, we found that differences in paralogs function was due to difference in the translation pattern. The minor paralog promoted the translation of cell wall genes with long open reading frames (ORFs), which are normally under-translated in the presence of the major paralog, leading to drug resistance. Reducing the ORF length repressed the minor paralog and staurosporine effects on translation. Together the data reveal a natural mechanism for the optimization of translation through changes in the identity of ribosomal protein genes.

2020-03-09 | GSE133457 | GEO

E.coli Ribosome protein composition

Project description:Ribosomes are essential macromolecular complexes conducting protein biosynthesis in all domains of life. Cells can have heterogeneous ribosomes, i.e. ribosomes with various ribosomal RNA (rRNA) and ribosomal protein (r-protein) composition. However, the functional importance of heterogeneous ribosomes has remained elusive. One of the possible sources for ribosome heterogeneity is provided by paralogous r-proteins. In E. coli, ribosomal protein bL31 has two paralogs: bL31A encoded by rpmE and bL31B encoded by ykgM. This study investigates phenotypic effects of these ribosomal protein paralogs using bacterial strains expressing only bL31A or bL31B. We show that bL31A confers higher fitness to E. coli under lower temperatures. In addition, bL31A and bL31B have different effects on translation reading frame maintenance and apparent translation processivity in vivo as demonstrated by dual luciferase assay. In general, this study demonstrates that ribosomal protein paralog composition (bL31A versus bL31B) can affect cell growth and translation outcome.

2020-10-20 | PXD018123 | Pride

Extensive translation of small Open Reading Frames revealed by Poly-Ribo-Seq

Project description:We present a genome-wide assessment of small open reading frames (smORF) translation by ribosomal profiling of polysomal fractions in Drosophila S2 cell. In this way, mRNAs bound by multiple ribosomes and hence actively translated can be isolated and distinguished from mRNAs bound by sporadic, putatively non-productive single ribosomes or ribosomal subunits. Ribosomal profiling of large and small polysomal fractions in Drosophila S2 cells to assess translation of smORFs

2014-09-11 | E-GEOD-60384 | biostudies-arrayexpress

Cold Triggered Paralog Rearrangements Indicate Potential Ribosome Specialization in Arabidopsis thaliana

Project description:Plant ribosomes are heterogeneous due to genome duplications that resulted in several paralog genes encoding each ribosomal protein (RP). The mainstream view suggests that heterogeneity provides sufficient ribosomes throughout the Arabidopsis lifespan without any functional implications. Nevertheless, genome duplications are known to produce sub- and neofunctionalization of initially redundant genes. Functional divergence of RP paralogs can be considered ribosome specialization if the diversified functions of these paralogs remain within the context of protein translation, especially if RP divergence should contribute to a preferential or ultimately even rigorous selection of transcripts to be translated by a RP-defined ribosome subpopulation. Here we provide evidence that cold acclimation triggers a reprogramming in structural RPs at the transcriptome and proteome level. The reprogramming alters the abundance of RPs or RP paralogs in non-translational 60S large subunits (LSUs) and translational polysome fractions, a phenomenon known as substoichiometry. Cold triggered substoichiometry of ribosomal complexes differ once Arabidopsis REIL-like mediated late maturation step for the LSU is impaired. Interestingly, remodeling of ribosomes after a cold stimulus appears to be significantly constrained to specific spatial regions of the ribosome. The regions that are significantly changed during cold acclimation as judged by transcriptome or proteome data include the polypeptide exit tunnel and the P-Stalk. Both substructures of the ribosome represent plausible targets of mechanisms that may constrain translation by controlled ribosome heterogeneity. This work represents a step forward towards understanding heterogeneity and potential specialization of plant ribosomal complexes.

2021-06-28 | PXD016292 | Pride

Transcription profiling of S. cerevisiae ribosomal protein knockouts

Project description:Duplicated genes escape gene loss by conferring a dosage benefit or evolving diverged functions. The yeast Saccharomyces cerevisiae contains many duplicated genes encoding ribosomal proteins. Prior studies have suggested that these duplicated proteins are functionally redundant and affect cellular processes in proportion to their expression. In contrast, through studies of ASH1 mRNA in yeast, we demonstrate paralog-specific requirements for the translation of localized mRNAs. Intriguingly, these paralog-specific effects are limited to a distinct subset of duplicated ribosomal proteins. Moreover, transcriptional and phenotypic profiling of cells lacking specific ribosomal proteins reveals differences between the functional roles of ribosomal protein paralogs that extend beyond effects on mRNA localization. Finally, we show that ribosomal protein paralogs exhibit differential requirements for assembly and localization. Together, our data indicate complex specialization of ribosomal proteins for specific cellular processes, and support the existence of a ribosomal code. Experiment Overall Design: We used Affymetrix arrays to analyze the transcriptional profiles of cells lacking certain duplicated ribosomal protein genes in order to determine if paralogous ribosomal proteins have differing cellular effects and roles. Experiment Overall Design: Two biological replicates were performed for each strain. Each ribosomal protein deletion was then compared to the isogenic wild-type strain.

2008-06-16 | E-GEOD-8761 | biostudies-arrayexpress

RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function

Project description:Although several ribosomal protein (RP) paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes (RPL3L-ribosomes) in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide new insight into the mechanisms and physiological relevance of tissue-specific translational regulation.

2023-03-15 | GSE203072 | GEO

Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes

Project description:Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be non-coding, including 5' UTRs and lncRNAs. Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames (ORFs). Here we show hallmarks of translation in these footprints: co-purification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including induction of immune responses following human cytomegalovirus (HCMV) infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts to understand how cells manage and exploit its consequences. Ribosome profiling to verify that true ribosome footprints shift in response to different elongation inhibitors (CHX vs Emetine) and co-purify with an affinity-tagged large ribosomal subunit (bound vs input)

2014-08-21 | E-GEOD-60095 | biostudies-arrayexpress

Extensive translation of small Open Reading Frames revealed by Poly-Ribo-Seq

2014-09-11 | GSE60384 | GEO

Transcriptional profiling of ribosomal protein knockouts

2007-11-06 | GSE8761 | GEO