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Alternative splicing events driven by altered levels of Gemin5 undergo translation

ABSTRACT: Alternative splicing events driven by altered levels of Gemin5 undergo translation

PROVIDER: PRJNA1087300 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28330509_1.fastq.gz	Fastqsanger.gz
	SRR28330509_2.fastq.gz	Fastqsanger.gz
	SRR28330510_1.fastq.gz	Fastqsanger.gz
	SRR28330510_2.fastq.gz	Fastqsanger.gz
	SRR28330511_1.fastq.gz	Fastqsanger.gz

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Alternative splicing events driven by altered levels of Gemin5 undergo translation

Project description:We show that upregulation of Gemin5 can be detrimental as it modifies the steady state of mRNAs and enhances alternative splicing (AS) events of genes involved in a broad range of cellular processes. RNA-Seq analyses of the mRNA associated with polysomes in cells with high levels of Gemin5 revealed that a significant fraction of the differential AS events was enriched in polysomes.

2024-08-19 | GSE261488 | GEO

RNA maps of the non-canonical RNA-binding site of Gemin5

Project description:We report the CLIP-seq data of the non-canonical RNA-binding site of Gemin5. This region consists of two domains, RBS1 and RBS2, differing in their RNA-interaction features. Interestingly, the most abundant RNA target of the RBS1 polypeptide was the Gemin5 mRNA. Biochemical and functional characterization of this target demonstrated that RBS1 domain physically interacts with a stem-loop upregulating mRNA translation by counteracting the negative effect of Gemin5 protein on global protein synthesis. We propose that the RBS1 domain of Gemin5 performs a dual role on translation control, which depends on the target RNA, allowing fine-tune the availability of Gemin5 to play its multiple roles in gene expression control

2018-08-30 | GSE102268 | GEO

Cell type specific profiling of alternative translation identifies novel protein isoforms in the mouse brain

Project description:Translation canonically begins at a single AUG and terminates at the stop codon, generating one protein species per transcript. However, some transcripts may use alternative initiation sites or sustain translation past their stop codon, generating multiple protein isoforms. Through other mechanisms such as alternative splicing, both neurons and glia exhibit remarkable transcriptional diversity, and these other forms of post-transcriptional regulation are impacted by neural activity and disease. Here, using ribosome footprinting, we demonstrate that alternative translation is likewise abundant in the central nervous system and modulated by stimulation and disease. First, in neuron/glia mixed cultures we identify hundreds of transcripts with alternative initiation sites and confirm the protein isoforms corresponding to a subset of these sites by mass spectrometry. Many of them modulate their alternative initiation in response to KCl stimulation, indicating activity-dependent regulation of this phenomenon. Next, we detect several transcripts undergoing stop codon readthrough thus generating novel C-terminally-extended protein isoforms in vitro. Further, by coupling Translating Ribosome Affinity Purification to ribosome footprinting to enable cell-type specific analysis in vivo, we find that several of both neuronal and astrocytic transcripts undergo readthrough in the mouse brain. Functional analyses of one of these transcripts, Aqp4, reveals readthrough confers perivascular localization, indicating readthrough can be a conserved mechanism to modulate protein function. Finally, we show that AQP4 readthrough is disrupted in multiple gliotic disease models. Our study demonstrates the extensive and regulated use of alternative translational events in the brain and indicates that some of these events alter key protein properties. [NOTE: this GEO series only contains in vivo data]

2019-01-14 | GSE115483 | GEO

Gemin5-dependent RNA association to polysomes supports selective translation of mRNA subsets

Project description:Here we report the identification at a genome-wide scale of the mRNAs associated to polysomes in Gemin5-depleted cells relative to control cells. Among the polysomal Gemin5-enhanced mRNAs, we identified numerous transcripts belonging to two distinct families, which encode ribosomal proteins and histones.

2022-08-24 | GSE200388 | GEO

Gemin5-dependent RNA association to polysomes supports selective translation of mRNA subsets

Project description:Gemin5-dependent RNA association to polysomes supports selective translation of mRNA subsets

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N6-Methyladenosine Guides mRNA Alternative Translation during Integrated Stress Response

Project description: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. Here we report that,in response to amino acid starvation, the reinitiation of ATF4 is not only governed by eIF2α-controlled ternary complex availability, but is also subjected to regulation by mRNA methylation in the form of N6-methyladenosine (m6A). We demonstrate that m6A in the 5' untranslated region (5’ UTR) controls ribosome scanning and subsequent start codonselection. Global profiling of initiating ribosomes reveals widespread alternative translation events influenced by mRNA methylation. Consistently, Fto-transgenic mice manifest enhanced ATF4 expression, highlighting the critical role of 5’ UTR methylation in translational regulation of ISR at cellular and organismal levels.

2017-08-15 | GSE102659 | GEO

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Profiling of alternative polyadenylation events in Arabidopsis thaliana

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Selective translation by alternative bacterial ribosomes

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2019-04-11 | GSE127827 | GEO

Alternative 3’UTRs play a widespread role in translation-independent mRNA association with endoplasmic reticulum

Project description:Transcripts encoding membrane and secreted proteins are known to undergo translation on endoplasmic reticulum (ER). Translation-independent ER association (TiERA) has been reported for certain mRNAs, but the phenomenon is poorly understood. Here, using cell fractionation, polysome profiling, and 3’ end sequencing, we examine TiERA of poly(A)+ RNAs in mouse C2C12 myoblast cells. We identify transcript features that facilitate TiERA, including transcript size and GG and GC content. Consistent with the feature analysis, alternative polyadenylation (APA) isoforms differ substantially in TiERA, with long 3’UTR isoforms generally having a higher TiERA potential than short 3’UTR isoforms. Importantly, the widespread 3’UTR lengthening taking place in cell differentiation leads to greater transcript association with ER in differentiated myotubes, despite that the TiERA potential being generally maintained. In addition, we show that TiERA correlates negatively with mRNA stability, highlighting 3’UTR-mediated mRNA decay on ER. Together, our data indicate that sequence and size features impact ER association independent of translation, leading to distinct mRNA metabolism for different transcript groups, and APA can alter transcript stability and translation through isoform-specific ER association.

2021-07-20 | GSE162971 | GEO

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