HnRNP L protects mRNAs from nonsense-mediated mRNA decay
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109143 | GEO | 2018/12/05
REPOSITORIES: GEO
Similar Datasets
Project description:hnRNP L protects mRNAs from nonsense-mediated mRNA decay
| PRJNA429768 | ENA
Project description:RNA-seq analysis of human 293 Tet-off cells depleted of PTBP1 and UPF1 alone and in tandem with specific siRNAs.
2016-01-21 | GSE59884 | GEO
Project description:We have HA-tagged two nonsense-mediated decay proteins, UPF1 and UPF2, in the malaria parasite Plasmodium falciparum. We then performed co-immunoprecipitation experiments to determine the protein-protein interactions of these nonsense-mediated decay components.
2021-04-16 | PXD023910 | Pride
Project description:RNA quality control pathways serve to get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the ATPase cycle of SF1 Helicase Upf1 is required for mRNA discrimination during Nonsense-Mediated Decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD - translation and termination codon-proximal poly(A) binding protein - depend on Upf1 ATPase to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase-dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be an underappreciated, yet widely employed, activity in target RNA discrimination. CLIP and RIP-seq against Wild Type and Mutant Upf1 in HEK293-T cell lines
2015-07-06 | E-GEOD-69584 | biostudies-arrayexpress
Project description:RNA quality control pathways serve to get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the ATPase cycle of SF1 Helicase Upf1 is required for mRNA discrimination during Nonsense-Mediated Decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD - translation and termination codon-proximal poly(A) binding protein - depend on Upf1 ATPase to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase-dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be an underappreciated, yet widely employed, activity in target RNA discrimination. CLIP and RIP-seq against Wild Type and Mutant Upf1 in HEK293-T cell lines
2015-07-06 | E-GEOD-69585 | biostudies-arrayexpress
Project description:Multiple studies showed that overexpression of UPF1 reduced the growth of HCC. However, it remains unanswered how UPF1 expression retarded HCC proliferation. Thus, this study employed UPF1 variants to evaluate the UPF1 function in HCC growth inhibition. Transcriptome analysis indicated that the level of DUSP1, dual specificity phosphatase 1, was upregulated by UPF1 variants by posttranscriptional regulation. The increase of DUPS1 by UPF1 overexpression repressed the downstream signaling, inhibiting cell growth.
2021-10-13 | GSE185655 | GEO
Project description:RNA quality control pathways serve to get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the ATPase cycle of SF1 Helicase Upf1 is required for mRNA discrimination during Nonsense-Mediated Decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD - translation and termination codon-proximal poly(A) binding protein - depend on Upf1 ATPase to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase-dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be an underappreciated, yet widely employed, activity in target RNA discrimination.
2015-07-06 | GSE69585 | GEO
Project description:RNA quality control pathways serve to get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the ATPase cycle of SF1 Helicase Upf1 is required for mRNA discrimination during Nonsense-Mediated Decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD - translation and termination codon-proximal poly(A) binding protein - depend on Upf1 ATPase to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase-dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be an underappreciated, yet widely employed, activity in target RNA discrimination.
2015-07-06 | GSE69584 | GEO
Project description:The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD.
| S-EPMC4764554 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is a deleterious neurodegenerative disease without effective treatment options. Recent studies have indicated the involvement of the dysregulation of RNA metabolism in the pathogenesis of ALS. Among the various RNA regulatory machineries, nonsense-mediated mRNA decay (NMD) is a stress responsive cellular surveillance system that degrades selected mRNA substrates to prevent the translation of defective or harmful proteins. Whether this pathway is affected in neurodegenerative diseases is unclear. Here we report that the NMD pathway is inhibited in ALS patients with C9orf72 hexanucleotide repeat expansion (HRE), the most common cause of familial ALS. Bioinformatic analysis of multiple transcriptome profiles revealed significant overlap of upregulated genes in NMD-defective cells with those in the brain tissues, micro-dissected motor neurons, or induced pluripotent stem cell-derived motor neurons from ALS patients carrying C9orf72 HRE, suggesting the suppression of NMD pathway in these patients. In contrast, there are few overlapping upregulated genes in brain tissues from sporadic ALS patients with those in NMD-defective cells. Using Drosophila models expressing various C9orf72 HRE products, we have validated the suppression of the NMD pathway by C9orf72 HRE and identified arginine-rich dipeptide repeats (DPRs) generated from HRE as the main culprits of NMD inhibition. Furthermore, in human SH-SY5Y neuroblastoma cells and in mouse brains, expression of arginine-rich DPRs was sufficient to cause NMD inhibition. Remarkably, expression of UPF1, a core gene in the NMD pathway, efficiently blocked neurotoxicity caused by arginine-rich DPRs in both cellular and Drosophila models. Although not as effective as UPF1, expression of another NMD gene UPF2 also ameliorated the degenerative phenotypes in DPR-expressing flies, indicating neuroprotection by genetically reactivating the NMD pathway. Finally, after validating Tranilast as an NMD-activating drug, we demonstrated its therapeutic potential in cellular and Drosophila models of C9orf72 DPR neurotoxicity. Therefore, our study has revealed the suppression of NMD in C9orf72 ALS and has suggested that the restoration of the NMD pathway by Tranilast, an asthma drug with solid safety record, could be a promising therapeutic strategy for ALS.
2018-12-01 | GSE123172 | GEO