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C Eno, C L Hansen, F Pelegri
BACKGROUND: In zebrafish and many other organisms, specification of primordial germ cells (PGCs) requires the transmission of maternally-derived germ plasm. Zebrafish germ plasm ribonucleoparticles (RNPs) aggregate along the cleavage furrows during the first several cell cycles, segregate asymmetrically during the cleavage stages, and undergo cytoplasmic dispersal in the late blastula. RESULTS: For all tested germ plasm RNAs [carbonic anhydrase 15b (ca15b), deleted in azoospermia-like (dazl), dead end (dnd), nanos 3 (nos3), regulator of G-protein signaling14a (rgs14a), and vasa/DEAD box polypeptide 4 (vasa/ddx4)], RNPs are homotypic (containing a single RNA type), with RNPs packing tightly yet remaining distinct within germ plasm aggregates...
February 11, 2019: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Pantelis Nicola, Patrick R Blackburn, Kristen J Rasmussen, Nicole L Bertsch, Eric W Klee, Linda Hasadsri, Pavel N Pichurin, Julia Rankin, F Lucy Raymond, Jill Clayton-Smith
DDX3X (Xp11.4) encodes a DEAD-box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in DDX3X have been shown to cause X-linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated with DDX3X variants are heterogeneous and include brain and behavioral abnormalities, microcephaly, hypotonia, and movement disorders and/or spasticity. The majority of DDX3X variants described are de novo mutations in females with ID. In contrast, most male DDX3X variants are inherited from an unaffected mother, with one documented exception being a recently identified de novo splice site variant...
February 7, 2019: American Journal of Medical Genetics. Part A
Annalaura Brai, Francesco Martelli, Valentina Riva, Anna Garbelli, Roberta Fazi, Claudio Zamperini, Alessandro Pollutri, Lucia Falsitta, Stefania Ronzini, Laura Maccari, Giovanni Maga, Simone Giannecchini, Maurizio Botta
Increased frequency of arbovirus outbreaks in the last ten years represents an important emergence for global health. Climate warming, extensive urbanization of tropical regions and human migrations flows facilitate the expansion of anthropophilic mosquitos and the emerging or re-emerging of new viral infections. Only recently the human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against infectious diseases. Herein, starting from our previous studies a new family of DDX3X inhibitors was designed, synthesized, validated on the target enzyme and evaluated against West Nile Virus (WNV) infection...
February 5, 2019: Journal of Medicinal Chemistry
C-M Xu, L-X Chen, F Gao, M-F Zhu, Y Dai, Y Xu, W-X Qian
OBJECTIVE: We aimed to detect the role and function of microRNA-431 (miR-431) in lung cancer, and to investigate the underlying mechanism in regulating the development of lung cancer. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to measure the relative expression level of miR-431 in lung cancer tissues and cell lines. Cell counting kit-8 (CCK-8) and colony formation assays were employed to measure the proliferative ability of lung cancer cells...
January 2019: European Review for Medical and Pharmacological Sciences
Sridevi Nidumukkala, Lavanya Tayi, Rajani Kant Chittela, Dashavantha Reddy Vudem, Venkateswara Rao Khareedu
Diverse abiotic stresses constitute one of the major factors which adversely affect the normal plant growth and development which results worldwide in decreased agricultural productivity. At present, utilization of new molecular tools to achieve improved stress tolerance and increased crop productivity is highly desirable. Abiotic stress in plants induces expression of a wide range of genes like transcription factors, defense related genes and so on, and the products of these genes are important in combating stress conditions...
February 3, 2019: Critical Reviews in Biotechnology
Yueh-Chun Lee, Wen-Ling Wang, Wei-Chao Chang, Yu-Hao Huang, Guan-Ci Hong, Hui-Lin Wang, Ying-Hsiang Chou, Hsien-Chun Tseng, Hsueh-Te Lee, Shao-Ti Li, Hsin-Lin Chen, Chun-Chieh Wu, Huei-Fan Yang, Bing-Yen Wang, Wen-Wei Chang
Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy...
January 22, 2019: Cancers
Ruchika Sachdev, Maria Hondele, Miriam Linsenmeier, Pascal Vallotton, Christopher F Mugler, Paolo Arosio, Karsten Weis
Processing bodies (PBs) are cytoplasmic mRNP granules that assemble via liquid-liquid phase separation and are implicated in the decay or storage of mRNAs. How PB assembly is regulated in cells remains unclear. Previously, we identified the ATPase activity of the DEAD-box protein Dhh1 as a key regulator of PB dynamics and demonstrated that Not1, an activator of the Dhh1 ATPase and member of the CCR4-NOT deadenylase complex inhibits PB assembly in vivo (Mugler et al., 2016). Here, we show that the PB component Pat1 antagonizes Not1 and promotes PB assembly via its direct interaction with Dhh1...
January 16, 2019: ELife
Chunxing Yang, Daojiang Li, Yang Bai, Shenglei Song, Peicheng Yan, Runliu Wu, Yi Zhang, Gui Hu, Changwei Lin, Xiaorong Li, Lihuang Huang
Background: Cancer stem cells (CSCs) are responsible for all important characteristics of tumors. DEAD-box helicase 27 (DDX27) is a member of the DEAD-box RNA helicase family, and there have been only a few studies on DDX27 function in cancer cells. This study is aimed at exploring whether DDX27 has any relation to tumorigenesis of colorectal cancer (CRC) and elucidating the potential mechanism. Methods: Data from Catalog Of Somatic Mutations In Cancer, Gene Expression Omnibus, and The Cancer Genome Atlas databases reveal that DDX27 is overexpressed in CRC tissues...
2019: OncoTargets and Therapy
Ghazala Nawaz, Hunseung Kang
BACKGROUND: Despite increasing characterization of DEAD-box RNA helicases (RHs) in chloroplast gene expression regulation at posttranscriptional levels in plants, their functional roles in growth responses of crops, including rice (Oryza sativa), to abiotic stresses are yet to be characterized. In this study, rice OsRH58 (LOC_Os01g73900), a chloroplast-localized DEAD-box RH, was characterized for its expression patterns upon stress treatment and its functional roles using transgenic Arabidopsis plants under normal and abiotic stress conditions...
January 9, 2019: BMC Plant Biology
Sivabalan Karthik, Narendra Tuteja, Andy Ganapathi, Markandan Manickavasagam
Protein p68 is a prototype constituent of DEAD-box protein family, which is involved in RNA metabolism, induced during abiotic stress conditions. In order to address the salinity stress faced by economically important soybean crop, we have transformed soybean cv. PUSA 9712 via direct organogenesis with marker free construct of p68 gene by Agrobacterium -mediated genetic transformation. The putative transgenic plants were screened by Polymerase chain reaction (PCR), Dot blot analysis and Southern blot hybridization...
January 2019: 3 Biotech
Guo-Qin Li, Yong Tian, Li Chen, Jun-da Shen, Zheng-Rong Tao, Tao Zeng, Jian Xu, Li-Zhi Lu
1. Melanoma differentiation-associated gene 5 (MDA5) is a critical member of cytosolic pattern recognition receptors (PRRs) that recognise viral RNA and mediate type I interferon secretion in host cells. 2. The objective of the present study was to identify and characterise the structure and expression of pigeon MDA5. 3. The full-length MDA5 cDNA was cloned from pigeon spleen using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The distribution and expression level of pigeon MDA5 in different tissues were determined by quantitative real-time PCR (QRT-PCR)...
December 30, 2018: British Poultry Science
Feng Yang, Erhu Fang, Hong Mei, Yajun Chen, Huanhuan Li, Dan Li, Huajie Song, Jianqun Wang, Mei Hong, Wenjing Xiao, Xiaojing Wang, Kai Huang, Liduan Zheng, Qiangsong Tong
Circular RNAs (circRNA), a subclass of noncoding RNA characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. However, the functions and underlying mechanisms of circRNA in regulating Wnt/β-catenin signaling and cancer progression remain elusive. Here we screen cis-acting circRNA generated by β-catenin (CTNNB1)/transcription factor 7 like 2 genes and identify one intronic circRNA derived from CTNNB1 (circ-CTNNB1) as a novel driver of cancer progression...
December 18, 2018: Cancer Research
Martyna O Urbanek-Trzeciak, Edyta Jaworska, Wlodzimierz J Krzyzosiak
MicroRNAs (miRNAs) are short, non-coding post-transcriptional gene regulators. In mammalian cells, mature miRNAs are produced from primary precursors (pri-miRNAs) using canonical protein machinery, which includes Drosha/DGCR8 and Dicer, or the non-canonical mirtron pathway. In plant cells, mature miRNAs are excised from pri-miRNAs by the DICER-LIKE1 (DCL1) protein complex. The involvement of multiple regulatory proteins that bind directly to distinct miRNA precursors in a sequence- or structure-dependent manner adds to the complexity of the miRNA maturation process...
December 17, 2018: International Journal of Molecular Sciences
Nana Aduma, Hiroe Izumi, Shusei Mizushima, Asato Kuroiwa
DEAD-box helicase 4 (DDX4; also known as vasa) is essential for the proper formation and maintenance of germ cells. Although DDX4 is conserved in a variety of vertebrates and invertebrates, its roles differ between species. This study investigated the function of DDX4 in chicken embryos by knocking down its expression using retroviral vectors that encoded DDX4-targeting microRNAs. DDX4 was effectively depleted in vitro and in vivo via this approach. Male and female gonads of DDX4-knockdown embryos contained a decreased number of primordial germ cells, indicating that DDX4 is essential to maintain a normal level of these cells in chicken embryos of both sexes...
December 17, 2018: Reproduction, Fertility, and Development
Zheng Xing, Wai Kit Ma, Elizabeth J Tran
The mammalian DEAD-box RNA helicase DDX5, its paralog DDX17, and their orthologs in Saccharomyces cerevisiae and Drosophila melanogaster, namely Dbp2 and Rm62, define a subfamily of DEAD-box proteins. Members from this subfamily share highly conserved protein sequences and cellular functions. They are involved in multiple steps of RNA metabolism including mRNA processing, microRNA processing, ribosome biogenesis, RNA decay, and regulation of long noncoding RNA activities. The DDX5/Dbp2 subfamily is also implicated in transcription regulation, cellular signaling pathways, and energy metabolism...
December 2, 2018: Wiley Interdisciplinary Reviews. RNA
Ali AbuMadighem, Ronnie Solomon, Alina Stepanovsky, Joseph Kapelushnik, QingHua Shi, Eckart Meese, Eitan Lunenfeld, Mahmoud Huleihel
Aggressive chemotherapy may lead to permanent male infertility. Prepubertal males do not generate sperm, but their testes do contain spermatogonial cells (SPGCs) that could be used for fertility preservation. In the present study, we examined the effect of busulfan (BU) on the SPGCs of immature mice, and the possible induction of the survivor SPGCs to develop spermatogenesis in 3D in-vitro culture. Immature mice were injected with BU, and after 0.5⁻12 weeks, their testes were weighed and evaluated histologically compared to the control mice...
November 29, 2018: International Journal of Molecular Sciences
Linh Vu Nguyen, Hye-Yeon Seok, Dong-Hyuk Woo, Sun-Young Lee, Yong-Hwan Moon
Plants adapt to abiotic stresses by complex mechanisms involving various stress-responsive genes. Here, we identified a DEAD-box RNA helicase (RH) gene, AtRH17 , in Arabidopsis , involved in salt-stress responses using activation tagging, a useful technique for isolating novel stress-responsive genes. AT895, an activation tagging line, was more tolerant than wild type (WT) under NaCl treatment during germination and seedling development, and AtRH17 was activated in AT895. AtRH17 possesses nine well-conserved motifs of DEAD-box RHs, consisting of motifs Q, I, Ia, Ib, and II-VI...
November 28, 2018: International Journal of Molecular Sciences
Nan Wu, Mingzuo Jiang, Yuying Han, Haiming Liu, Yi Chu, Hao Liu, Jiayi Cao, Qiuqiu Hou, Yu Zhao, Bing Xu, Xin Xie
The RNA helicase p68 (DDX5), a key player in RNA metabolism, belongs to the DEAD box family and is involved in the development of colorectal cancer. Here, we found both DDX5 and O-GlcNAcylation are up-regulated in colorectal cancer. In addition, DDX5 protein level is significantly positively correlated with the expression of O-GlcNAcylation. Although it was known DDX5 protein could be regulated by post-translational modification (PTM), how O-GlcNAcylation modification regulated of DDX5 remains unclear. Here we show that DDX5 interacts directly with OGT in the SW480 cell line, which is the only known enzyme that catalyses O-GlcNAcylation in humans...
November 28, 2018: Journal of Cellular and Molecular Medicine
Eckhard Jankowsky, Ulf-Peter Guenther
Upstream open reading frames (uORFs) in 5' UTRs of eukaryotic mRNAs are increasingly recognized as important elements that regulate cellular protein synthesis. Since uORFs can start from non-AUG codons, an enormous number of potential uORF initiation sites exists in 5'UTRs. However, only a subset of these sites is used and it has been unclear how actual start sites are selected. Studies of the DEAD-box helicase Ded1p from S. cerevisiae show that translation of uORFs with non-AUG initiation codons occurs upstream of mRNA structures that emerge with defective Ded1p...
November 27, 2018: Current Genetics
Daniel Szappanos, Roland Tschismarov, Thomas Perlot, Sandra Westermayer, Katrin Fischer, Ekaterini Platanitis, Fabian Kallinger, Maria Novatchkova, Caroline Lassnig, Mathias Müller, Veronika Sexl, Keiryn L Bennett, Michelle Foong-Sobis, Josef M Penninger, Thomas Decker
DExD/H box RNA helicases, such as the RIG-I-like receptors (RLR), are important components of the innate immune system. Here we demonstrate a pivotal and sex-specific role for the heterosomal isoforms of the DEAD box RNA helicase DDX3 in the immune system. Mice lacking DDX3X during hematopoiesis showed an altered leukocyte composition in bone marrow and spleen and a striking inability to combat infection with Listeria monocytogenes. Alterations in innate immune responses resulted from decreased effector cell availability and function as well as a sex-dependent impairment of cytokine synthesis...
November 26, 2018: PLoS Pathogens
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