scholarly journals The role of RNA helicases in aging and lifespan regulation

2017 ◽  
Vol 1 ◽  
pp. 24-31 ◽  
Author(s):  
Sangsoon Park ◽  
Hae-Eun H. Park ◽  
Heehwa G. Son ◽  
Seung-Jae V. Lee
2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Yanni Xu ◽  
Qiongchao Jiang ◽  
Hejun Liu ◽  
Xiaoyun Xiao ◽  
Dinghong Yang ◽  
...  

Background. RNA helicases have various essential functions in basically all aspects of RNA metabolism, not only unwinding RNA but also disturbing the interaction of RNA with proteins. Recently, RNA helicases have been considered potential targets in cancers. So far, there has been no detailed investigation of the biological functions of RNA helicase DHX37 in cancers. Objective. We aim to identify the prognostic value of DHX37 associated with tumor microenvironments in cancers. Methods. DHX37 expression was examined via the Oncomine database and Tumor Immune Estimation Resource (TIMER). We explored the prognostic role of DHX37 in cancers across various databases. Coexpression genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and fundamental regulators were performed via LinkedOmics. Confirming the prognostic value of DHX37 in liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD), we explored the role of DHX37 in infiltrated lymphocytes in cancers using the Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases. Results. Through GO and KEGG analyses, expression of DHX37 was also correlated with complex function-specific networks involving the ribosome and RNA metabolic signaling pathways. In LIHC and LUAD, DHX37 expression showed significant positive correlations with markers of Tregs, myeloid-derived suppressor cells (MDSCs), and T cell exhaustion, contributing to immune tolerance. Conclusion. These results indicate that DHX37 can serve as a prognostic biomarker in LIHC and LUAD while having an important role in immune tolerance by activating the function of Tregs, MDSC, and T cell exhaustion.


Oncogene ◽  
2012 ◽  
Vol 31 (42) ◽  
pp. 4536-4549 ◽  
Author(s):  
S Germann ◽  
L Gratadou ◽  
E Zonta ◽  
E Dardenne ◽  
B Gaudineau ◽  
...  

2019 ◽  
Vol 5 (8) ◽  
pp. eaax1031 ◽  
Author(s):  
Lei Bai ◽  
Jiazhen Dong ◽  
Zhenqiu Liu ◽  
Youliang Rao ◽  
Pinghui Feng ◽  
...  

Helicases play pivotal roles in fundamental biological processes, and posttranslational modifications regulate the localization, function, and stability of helicases. Here, we report that methionine oxidation of representative helicases, including DNA and RNA helicases of viral (ORF44 of KSHV) and cellular (MCM7 and RIG-I) origin, promotes their expression and functions. Cellular viperin, a major antiviral interferon-stimulated gene whose functions beyond host defense remain largely unknown, catalyzes the methionine oxidation of these helicases. Moreover, biochemical studies entailing loss-of-function mutations of helicases and a pharmacological inhibitor interfering with lipid metabolism and, hence, decreasing viperin activity indicate that methionine oxidation potently increases the stability and enzyme activity of these helicases that are critical for DNA replication and immune activation. Our work uncovers a pivotal role of viperin in catalyzing the methionine oxidation of helicases that are implicated in diverse fundamental biological processes.


2020 ◽  
Author(s):  
Hélène Scheer ◽  
Caroline de Almeida ◽  
Emilie Ferrier ◽  
Quentin Simonnot ◽  
Laure Poirier ◽  
...  

AbstractUridylation is a widespread modification destabilizing eukaryotic mRNAs. Yet, molecular mechanisms underlying TUTase-mediated mRNA degradation remain mostly unresolved. Here, we report that the Arabidopsis TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators. URT1 directly interacts with DECAPPING 5 (DCP5), the Arabidopsis ortholog of human LSM14 and yeast Scd6, and this interaction connects URT1 to additional decay factors like DDX6/Dhh1-like RNA helicases. Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. Based on in vitro and in planta data, we propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3’ terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development.


Author(s):  
Sorush Niknamian

Background: Approximately 80% of all viruses are RNA viruses and they contain their specific RNA helicases. Defective RNA helicases have been linked to infectious diseases (Viral Infections). Materials and Methods: The articles have gone through many types of research from the beginning of the epidemic of Coronaviruses through history and we introduced the neglected hypothesis of Shifting balance theory, Bateson-DobzhanskyMuller model & Quantum evolution. In the ancestral population, the genotype is AABB. When two populations become isolated from each other, new mutations can arise. In one population A evolves into a, and in the other B evolves into b. When the two populations hybridize it is the first time A and B interact with each other. When these alleles are incompatible, we speak of Dobzhansky–Muller incompatibilities plus the role of MMA in mitochondria in spreading SARS-CoV-19 through populations and the result of an infection in COVID-19. Results: In viruses specifically COVID-19, Ribosomal Frameshift is programmed to allows the virus to encode multiple types of proteins from the same mRNA. HIV-1 (human immunodeficiency virus), RSV (Rous sarcoma virus), and all types of influenza viruses use Ribosomal Frameshift. They rely on frameshifting to create a proper ratio of normal translation and trans-frame (encoded by frameshifted sequence) proteins. Notably, its use in viruses is primarily for compacting more genetic information into a shorter amount of genetic material. Conclusion: to find the genome sequence of COVID-19 we also used Nanopore sequencing that introduced and manufactured by Oxford scientists, due to differences in the action of infection in the host, we could not reach any results since the Novel Virus has not a stable genome (which is quite dynamic) since through our deep research, each virus contains its specific genome sequencing and we cannot claim that COVID-19 has one specific genome sequence like MERS-CoV, SARS-CoV or any types of viruses which has been discovered and contains their specific genome.


2019 ◽  
Vol 28 (15) ◽  
pp. 2561-2572 ◽  
Author(s):  
Raghuveer Kavarthapu ◽  
Rajakumar Anbazhagan ◽  
Murugananthkumar Raju ◽  
Chon-Hwa Tsai Morris ◽  
James Pickel ◽  
...  

Abstract Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis specific member of the DEAD-box family of RNA helicases expressed in meiotic and haploid germ cells which plays an essential role in spermatogenesis. There are two species of GRTH the 56 kDa non-phospho and 61 kDa phospho forms. Our early studies revealed a missense mutation (R242H) of GRTH in azoospermic men that when expressed in COS1-cells lack the phospho-form of GRTH. To investigate the role of the phospho-GRTH species in spermatogenesis, we generated a GRTH knock-in (KI) transgenic mice with the R242H mutation. GRTH-KI mice are sterile with reduced testis size, lack sperm with spermatogenic arrest at round spermatid stage and loss of the cytoplasmic phospho-GRTH species. Electron microscopy studies revealed reduction in the size of chromatoid bodies (CB) of round spermatids (RS) and germ cell apoptosis. We observed absence of phospho-GRTH in the CB of RS. Complete loss of chromatin remodeling and related proteins such as TP2, PRM2, TSSK6 and marked reduction of their respective mRNAs and half-lives were observed in GRTH-KI mice. We showed that phospho-GRTH has a role in TP2 translation and revealed its occurrence in a 3′ UTR dependent manner. These findings demonstrate the relevance of phospho-GRTH in the structure of the chromatoid body, spermatid development and completion of spermatogenesis and provide an avenue for the development of a male contraceptive.


Author(s):  
Rajakumar Anbazhagan ◽  
Raghuveer Kavarthapu ◽  
Steven L. Coon ◽  
Maria L. Dufau

GRTH/DDX25 is a member of the DEAD-box family of RNA helicases that play an essential role in spermatogenesis. GRTH knock-in (KI) mice with the human mutant GRTH gene (R242H) show loss of the phospho-species from cytoplasm with preservation of the non-phospho form in the cytoplasm and nucleus. GRTH KI mice are sterile and lack elongated spermatids and spermatozoa, with spermatogenic arrest at step 8 of round spermatids which contain chromatoid body (CB) markedly reduced in size. We observed an absence of phospho-GRTH in CB of GRTH KI mice. RNA-Seq analysis of mRNA isolated from CB revealed that 1,421 genes show differential abundance, of which 947 genes showed a decrease in abundance and 474 genes showed an increase in abundance in GRTH KI mice. The transcripts related to spermatid development, differentiation, and chromatin remodeling (Tnp1/2, Prm1/2/3, Spem1/2, Tssk 2/3/6, Grth, tAce, and Upf2) were reduced, and the transcripts encoding for factors involved in RNA transport, regulation, and surveillance and transcriptional and translational regulation (Eef1a1, Ppp1cc, Pabpc1, Ybx3, Tent5b, H2al1m, Dctn2, and Dync1h1) were increased in the CB of KI mice and were further validated by qPCR. In the round spermatids of wild-type mice, mRNAs of Tnp2, Prm2, and Grth were abundantly co-localized with MVH protein in the CB, while in GRTH KI mice these were minimally present. In addition, GRTH binding to Tnp1/2, Prm1/2, Grth, and Tssk6 mRNAs was found to be markedly decreased in KI. These results demonstrate the importance of phospho-GRTH in the maintenance of the structure of CB and its role in the storage and stability of germ cell-specific mRNAs during spermiogenesis.


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