Search results for "DEAD-box RNA Helicases"
showing 10 items of 15 documents
Dual role of the RNA helicase DDX5 in post-transcriptional regulation of Myelin Basic Protein in oligodendrocytes
2017
In the central nervous system, oligodendroglial expression of Myelin Basic Protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly on the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (alias p68) in a complex with Mbp mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with Mbp mRNA in the cell body and processes. Manipulation of DDX5 protein amounts inversely affects levels of MBP protein. We present evid…
Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development.
2020
Summary De novo germline mutations in the RNA helicase DDX3X account for 1%–3% of unexplained intellectual disability (ID) cases in females and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here, we use human and mouse genetics and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development. We report the largest clinical cohort to date with DDX3X mutations (n = 107), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcom…
Insights into the inhibited form of the redox-sensitive SufE-like sulfur acceptor CsdE
2017
17 p.-8 fig.
DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites
2017
The endoribonuclease DICER facilitates chromatin decondensation during lesion recognition following UV exposure. Chitale and Richly show that DICER mediates the recruitment of the methyltransferase MMSET, which catalyzes the dimethylation of histone H4 at lysine 20 and facilitates the recruitment of the nucleotide excision repair factor XPA.
Sequential recruitment of the mRNA decay machinery to the iron-regulated protein Cth2 in Saccharomyces cerevisiae
2020
Post-transcriptional factors importantly contribute to the rapid and coordinated expression of the multiple genes required for the adaptation of living organisms to environmental stresses. In the model eukaryote Saccharomyces cerevisiae, a conserved mRNA-binding protein, known as Cth2, modulates the metabolic response to iron deficiency. Cth2 is a tandem zinc-finger (TZF)-containing protein that co-transcriptionally binds to adenine/uracil-rich elements (ARE) present in the 3′-untranslated region of iron-related mRNAs to promote their turnover. The nuclear binding of Cth2 to mRNAs via its TZFs is indispensable for its export to the cytoplasm. Although Cth2 nucleocytoplasmic transport is ess…
Dicer and drosha expression and response to bevacizumab-based therapy in advanced colorectal cancer patients.
2013
PURPOSE: The miRNA-regulating enzymes Dicer and Drosha exhibit aberrant expression in several cancer types. Dicer and Drosha play a crucial role during the angiogenetic process in vitro and, for Dicer, in vivo. We aimed to investigate the potential role of Dicer and Drosha in predicting response to Bevacizumab-based therapy in advanced colorectal cancer (CRC) patients. METHODS: Dicer and Drosha mRNA levels were analysed in formalin-fixed paraffin-embedded specimens from patients affected by advanced CRC treated with or without Bevacizumab-containing regimens (n=116 and n=50, respectively) and from patients with diverticulosis as control group (n=20). The experimental data were obtained usin…
Deregulation of dicer and mir-155 expression in liposarcoma
2015
Liposarcoma (LPS) is the most common soft tissue sarcoma. It has been demonstrated that mir-155 was the most overexpressed miRNA in well-differentiated LPS(WDLPS)/dedifferentiated LPS (DDLPS). The aim of this study is to evaluate the involvement of Dicer, Drosha and mir-155 in development of LPS and their possible role in stratification of different histological subtypes. Dicer, Drosha and mir-155 mRNA levels were analyzed in formalin-fixed paraffin-embedded specimens from patients diagnosed with 62 LPS and compared with samples of adipose tissues of healthy donors. The experimental data were obtained using qRT-PCR comparing Dicer, Drosha and mir-155 expression levels in tumor samples versu…
Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.
2014
The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemica…
Insights into mRNP biogenesis provided by new genetic interactions among export and transcription factors.
2012
Abstract Background The various steps of mRNP biogenesis (transcription, processing and export) are interconnected. It has been shown that the transcription machinery plays a pivotal role in mRNP assembly, since several mRNA export factors are recruited during transcription and physically interact with components of the transcription machinery. Although the shuttling DEAD-box protein Dbp5p is concentrated on the cytoplasmic fibrils of the NPC, previous studies demonstrated that it interacts physically and genetically with factors involved in transcription initiation. Results We investigated the effect of mutations affecting various components of the transcription initiation apparatus on the…
Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells
2010
Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, …