Alternative splicing events driven by altered levels of Gemin5 undergo translation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE261488 | GEO | 2024/08/19
REPOSITORIES: GEO
Similar Datasets
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
Project description:Here, we report the genome-wide analysis of snRNAs that are bound to Gemin5 upon protein synthesis inhibition. Upon protein synthesis inhibition, the SMN complex that has a crucial role in the biogenesis of snRNPs dissociates into its subunits, leaving Gemin5 alone. The existence of these subunits was confirmed using a proteomics approach. As Gemin5 has been previously reported to be the RNA-binding protein of the SMN complex, we obtained the sequence of all Gemin5 immunoprecipitated snRNAs. We found that snRNAs that were accumulated on Gemin5 contained extra genomic sequences at the 3'-end. We were thus able to identify novel precursors of all the snRNAs that have not been identified previously. This study also provides a detailed method for the characterization of in vivo captured RNPs using a ribo-proteomics approach. Investigation of snRNAs specifically associated with Gemin5 upon protein synthesis inhibition
2010-06-24 | E-GEOD-20751 | biostudies-arrayexpress
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
Project description:GEMIN5 is a critical component of snRNP assembly complex. Patients carrying novel autosomal recessive variants in the GEMIN5 gene showed symptoms of developmental delay, central hypotonia, and cerebellar ataxia which are distinct than classical spinal muscular atrophy. We performed RNA-seq analysis in iPSC-derived differentiated neurons with biallelic GEMIN5-H913R mutation to identify global alterations in various genes and pathways mediated by GEMIN5 mutations in patients.
2021-03-11 | GSE168622 | GEO
Project description:Here, we report the genome-wide analysis of snRNAs that are bound to Gemin5 upon protein synthesis inhibition. Upon protein synthesis inhibition, the SMN complex that has a crucial role in the biogenesis of snRNPs dissociates into its subunits, leaving Gemin5 alone. The existence of these subunits was confirmed using a proteomics approach. As Gemin5 has been previously reported to be the RNA-binding protein of the SMN complex, we obtained the sequence of all Gemin5 immunoprecipitated snRNAs. We found that snRNAs that were accumulated on Gemin5 contained extra genomic sequences at the 3'-end. We were thus able to identify novel precursors of all the snRNAs that have not been identified previously. This study also provides a detailed method for the characterization of in vivo captured RNPs using a ribo-proteomics approach.
2010-06-24 | GSE20751 | GEO
Project description:Identification of cellular proteins interacting with Gemin5 variants found in patients with neurological disorders. P85 C-terminal fragment of Gemin5 has been used to purify the protein complexes associated by Tandem Affinity Purification. The study has been performed using two biological replicates of each bait protein: p85-WT, the dimerization mutant p85-A951E, and the clinical variants p85-R1016C, p85-D1019E and p85-L1367P.
2022-04-06 | PXD028959 | Pride
Project description:Identification of cellular proteins interacting with Gemin5 phosphorylation mutants in T897 residue. We used the T897A mutant as phosphorylation defective protein and the T897E mutant as phosphomimetic. P85 C-terminal fragment of Gemin5 has been used to purify the protein complexes associated by Tandem Affinity Purification. The study has been performed using two biological replicates of each bait protein: p85-T897A and p85-T897E.
2023-03-11 | PXD035227 | Pride
Project description:In eukaryotic cells translation initiation occurs through two alternative mechanisms, a cap-dependent operating in the majority of mRNAs, and a 5'-end-independent driven by internal ribosome entry site (IRES) elements, specific for a subset of mRNAs. IRES elements recruit the translation machinery to an internal position in the mRNA through a mechanism involving the IRES structure and several trans-acting factors. Here, we identified Gemin5 protein bound to the foot-and-mouth disease virus (FMDV) and hepatitis C virus (HCV) IRES using two independent approaches, riboproteomic analysis and immunoprecipitation of photocrosslinked factors. Functional analysis performed in Gemin5 shRNA-depleted cells, or in in vitro translation reactions, revealed an unanticipated role of Gemin5 in translation control as a down-regulator of cap-dependent and IRES-driven translation initiation. Consistent with this, pull-down assays showed that Gemin5 forms part of two distinct complexes, a specific IRES-ribonucleoprotein complex and an IRES-independent protein complex containing eIF4E. Thus, beyond its role in snRNPs biogenesis, Gemin5 also functions as a modulator of translation activity.
| S-EPMC2632916 | biostudies-literature
Project description:RNA-binding proteins (RBPs) play a pivotal role in the lifespan of RNAs. The disfunction of RBPs is frequently the cause of cell disorders which are incompatible with life. Furthermore, the ordered assembly of RBPs and RNAs in ribonucleoprotein (RNP) particles determines the function of biological complexes, as illustrated by the survival of the motor neuron (SMN) complex. Defects in the SMN complex assembly causes spinal muscular atrophy (SMA), an infant invalidating disease. This multi-subunit chaperone controls the assembly of small nuclear ribonucleoproteins (snRNPs), which are the critical components of the splicing machinery. However, the functional and structural characterization of individual members of the SMN complex, such as SMN, Gemin3, and Gemin5, have accumulated evidence for the additional roles of these proteins, unveiling their participation in other RNA-mediated events. In particular, Gemin5 is a multidomain protein that comprises tryptophan-aspartic acid (WD) repeat motifs at the N-terminal region, a dimerization domain at the middle region, and a non-canonical RNA-binding domain at the C-terminal end of the protein. Beyond small nuclear RNA (snRNA) recognition, Gemin5 interacts with a selective group of mRNA targets in the cell environment and plays a key role in reprogramming translation depending on the RNA partner and the cellular conditions. Here, we review recent studies on the SMN complex, with emphasis on the individual components regarding their involvement in cellular processes critical for cell survival.
| S-EPMC7311978 | biostudies-literature
Project description:Gene expression control largely depends on ribonucleoprotein complexes regulating mRNA translation. Initiation of translation in mRNAs that overcome cap-dependent translation inhibition is often driven by internal ribosome entry site (IRES) elements, whose activity is regulated by multifunctional RNA-binding factors. Here we show that Gemin5 interacts preferentially with a specific domain of a viral IRES consisting of a hairpin flanked by A/U/C-rich sequences. RNA-binding assays using purified proteins revealed that Gemin5-IRES interaction depends on the C-terminal region of the protein. Consistent with this novel finding, the C-terminal region of Gemin5, but not the N-terminal region, impaired translation. Furthermore, RNA selective 2'hydroxyl acylation analysed by primer extension (SHAPE) reactivity demonstrated that addition of purified Gemin5 to IRES mRNA induced the specific protection of residues around the hairpin of the IRES element. We further demonstrate that Gemin5 out-competed SHAPE reactivity variations induced by the IRES-binding factor PTB, leading to a local conformational change in the IRES structure. Together, our data unveil the inhibitory mechanism of Gemin5 on IRES-mediated translation.
| S-EPMC3553989 | biostudies-literature