scholarly journals The RNA Degradation Pathway Regulates the Function of GAS5 a Non-Coding RNA in Mammalian Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55684 ◽  
Author(s):  
Hidenori Tani ◽  
Masaki Torimura ◽  
Nobuyoshi Akimitsu
2012 ◽  
Vol 40 (4) ◽  
pp. 836-841 ◽  
Author(s):  
Jonathan Houseley

Unstable non-coding RNAs are produced from thousands of loci in all studied eukaryotes (and also prokaryotes), but remain of largely unknown function. The present review summarizes the mechanisms of eukaryotic non-coding RNA degradation and highlights recent findings regarding function. The focus is primarily on budding yeast where the bulk of this research has been performed, but includes results from higher eukaryotes where available.


BioMedicine ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 27
Author(s):  
Nai-Wen Chang ◽  
Yi-Ping Huang

Background: The activation of peroxisome proliferator-activated receptor alpha (PPARα) has been shown to reprogram tumor metabolism and exhibits great potential for treating anti-oral tumorigenesis. Methods: In this study, we used a pathway-based strategy to explore possible functional pathways involved in the anticancer activity of PPARα in oral cancer cells through next-generation sequencing (NGS) and bioinformatic approaches. Results: We found that 3919 genes were upregulated and 1060 genes were downregulated through PPARα activation. These genes were mainly involved in the proteasomal, mRNA surveillance, spliceosomal, RNA transport, and RNA degradation pathways, as indicated by GO and KEGG enrichment analysis. Importantly, a total of 13 upregulated genes in the RNA degradation pathway were identified including 3 core exosome factor genes (RRP43, RRP42, and CSL4), 2 TRAMP complex genes (TRF4 and Mtr4), 2 exosome cofactor genes (RRP6 and MPP6), 2 CCR4-NOT complex genes (CNOT2 and CNOT3), 2 Ski complex genes (SKI2 and Ski3), 1 decapping complex gene (EDC4), and 1 gene involved in 5’ exoribonuclease activity (XRN1). Conclusion: Our findings suggest that the activation of PPARα to upregulate the RNA degradation pathway might provide a new strategy for oral cancer treatment.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Beatrice T. Laudenbach ◽  
Karsten Krey ◽  
Quirin Emslander ◽  
Line Lykke Andersen ◽  
Alexander Reim ◽  
...  

AbstractWhile viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5′-triphosphate (PPP-) group that impairs degradation by the canonical 5′-3′ degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5′-3′ exonuclease XRN1. NUDT2 removes 5′-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5′-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals.


2012 ◽  
Vol 25 (10) ◽  
pp. 1275-1285 ◽  
Author(s):  
Ming-Bo Wang ◽  
Chikara Masuta ◽  
Neil A. Smith ◽  
Hanako Shimura

RNA silencing plays a critical role in plant resistance against viruses, with multiple silencing factors participating in antiviral defense. Both RNA and DNA viruses are targeted by the small RNA-directed RNA degradation pathway, with DNA viruses being also targeted by RNA-directed DNA methylation. To evade RNA silencing, plant viruses have evolved a variety of counter-defense mechanisms such as expressing RNA-silencing suppressors or adopting silencing-resistant RNA structures. This constant defense–counter defense arms race is likely to have played a major role in defining viral host specificity and in shaping viral and possibly host genomes. Recent studies have provided evidence that RNA silencing also plays a direct role in viral disease induction in plants, with viral RNA-silencing suppressors and viral siRNAs as potentially the dominant players in viral pathogenicity. However, questions remain as to whether RNA silencing is the principal mediator of viral pathogenicity or if other RNA-silencing-independent mechanisms also account for viral disease induction. RNA silencing has been exploited as a powerful tool for engineering virus resistance in plants as well as in animals. Further understanding of the role of RNA silencing in plant–virus interactions and viral symptom induction is likely to result in novel anti-viral strategies in both plants and animals.


PLoS Genetics ◽  
2017 ◽  
Vol 13 (3) ◽  
pp. e1006686 ◽  
Author(s):  
Silvia Calo ◽  
Francisco E. Nicolás ◽  
Soo Chan Lee ◽  
Ana Vila ◽  
Maria Cervantes ◽  
...  

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2562
Author(s):  
Yan Zhang ◽  
Zhixiang Chen

Selective autophagy is a highly regulated degradation pathway for the removal of specific damaged or unwanted cellular components and organelles such as protein aggregates. Cargo selectivity in selective autophagy relies on the action of cargo receptors and adaptors. In mammalian cells, two structurally related proteins p62 and NBR1 act as cargo receptors for selective autophagy of ubiquitinated proteins including aggregation-prone proteins in aggrephagy. Plant NBR1 is the structural and functional homolog of mammalian p62 and NBR1. Since its first reports almost ten years ago, plant NBR1 has been well established to function as a cargo receptor for selective autophagy of stress-induced protein aggregates and play an important role in plant responses to a broad spectrum of stress conditions including heat, salt and drought. Over the past several years, important progress has been made in the discovery of specific cargo proteins of plant NBR1 and their roles in the regulation of plant heat stress memory, plant-viral interaction and special protein secretion. There is also new evidence for a possible role of NBR1 in stress-induced pexophagy, sulfur nutrient responses and abscisic acid signaling. In this review, we summarize these progresses and discuss the potential significance of NBR1-mediated selective autophagy in broad plant responses to both biotic and abiotic stresses.


2008 ◽  
Vol 416 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Maria V. Zabolotskaya ◽  
Dominic P. Grima ◽  
Ming-Der Lin ◽  
Tze-Bin Chou ◽  
Sarah F. Newbury

The exoribonuclease Xrn1 is widely recognised as a key component in the 5′–3′ RNA degradation pathway. This enzyme is highly conserved between yeast and humans and is known to be involved in RNA interference and degradation of microRNAs as well as RNA turnover. In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place. In this paper we show for the first time that Pacman, the Drosophila homologue of Xrn1, is localized in cytoplasmic particles in Drosophila testis cells. These particles are present in both the mitotically dividing spermatogonia derived from primordial stem cells and in the transcriptionally active spermatocytes. Pacman is co-localized with the decapping activator dDcp1 and the helicase Me31B (a Dhh1 homologue) in these particles, although this co-localization is not completely overlapping, suggesting that there are different compartments within these granules. Particles containing Pacman respond to stress and depletion of 5′–3′ decay factors in the same way as yeast P-bodies, and therefore are likely to be sites of mRNA degradation or storage. Pacman is shown to be required for normal Drosophila spermatogenesis, suggesting that control of mRNA stability is crucial in the testis differentiation pathway.


2007 ◽  
Vol 27 (10) ◽  
pp. 3651-3666 ◽  
Author(s):  
Justina D. McEvoy ◽  
Uta Kossatz ◽  
Nisar Malek ◽  
Jeffrey D. Singer

ABSTRACT Two distinct pathways for the degradation of mammalian cyclin E have previously been described. One pathway is induced by cyclin E phosphorylation and is dependent on the Cul1/Fbw7-based E3 ligase. The other pathway is dependent on the Cul3-based E3 ligase, but the mechanistic details of this pathway have yet to be elucidated. To establish the role of Cul3 in the degradation of cyclin E in vivo, we created a conditional knockout of the Cul3 gene in mice. Interestingly, the biallelic loss of Cul3 in primary fibroblasts derived from these mice results in increased cyclin E expression and reduced cell viability, paralleling the loss of Cul3 protein expression. Cell cycle analysis of viable, Cul3 hypomorphic cells shows that decreasing the levels of Cul3 increases both cyclin E protein levels and the number of cells in S phase. In order to examine the role of Cul3 in an in vivo setting, we determined the effect of deletion of the Cul3 gene in liver. This gene deletion resulted in a dramatic increase in cyclin E levels as well as an increase in cell size and ploidy. The results we report here show that the constitutive degradation pathway for cyclin E that is regulated by the Cul3-based E3 ligase is essential to maintain quiescence in mammalian cells.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Salma Sohrabi-Jahromi ◽  
Katharina B Hofmann ◽  
Andrea Boltendahl ◽  
Christian Roth ◽  
Saskia Gressel ◽  
...  

RNA degradation pathways enable RNA processing, the regulation of RNA levels, and the surveillance of aberrant or poorly functional RNAs in cells. Here we provide transcriptome-wide RNA-binding profiles of 30 general RNA degradation factors in the yeast Saccharomyces cerevisiae. The profiles reveal the distribution of degradation factors between different RNA classes. They are consistent with the canonical degradation pathway for closed-loop forming mRNAs after deadenylation. Modeling based on mRNA half-lives suggests that most degradation factors bind intact mRNAs, whereas decapping factors are recruited only for mRNA degradation, consistent with decapping being a rate-limiting step. Decapping factors preferentially bind mRNAs with non-optimal codons, consistent with rapid degradation of inefficiently translated mRNAs. Global analysis suggests that the nuclear surveillance machinery, including the complexes Nrd1/Nab3 and TRAMP4, targets aberrant nuclear RNAs and processes snoRNAs.


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