1,720,991 research outputs found
Meta’omics: Challenges and Applications
No full textMetagenomics and metatranscriptomics are emerging as key disciplines towards a fully understanding the complex relationships between living organisms belonging to different kingdoms [...
Quelling: post-transcriptional gene silencing guided by small RNAs in Neurospora crassa
No full textThe filamentous fungus Neurospora crassa is a model organism for the study of gene silencing. The most characterized gene silencing mechanism in this ascomycete is quelling, which occurs at the post-transcriptional level. Quelling is triggered by the introduction of transgenes and results in silencing of both transgenes and cognate endogenous mRNAs. Quelling is related to co-suppression, observed in plants, and RNA interference in animals; it requires an Argonaute protein and acts by generating small RNA molecules (about 25 nt long), which in turn target mRNAs to be silenced. It has been recently shown that quelling is needed for the taming of transposons but, unlike other model organisms, does not seem to play any role in heterochromatin assembly and maintenance
How RNAi machinery enters the world of telomerase
Full text linkHuman telomerase holoenzyme consists of the catalytic component TERT and the template RNA TERC. However, a network of accessory proteins plays key roles in its assembly, localization and stability. Defects in genes involved in telomerase biology affect the renewal of critical stem cell populations and cause disorders such as telomeropathies. Moreover, activation of telomerase in somatic cells allows neoplastic cells to proliferate indefinitely, thus contributing to tumorigenesis. For these reasons, identification of new players involved in telomerase regulation is crucial for the determination of novel therapeutic targets and biomarkers. In the very last years, increasing evidence describe components of the RNAi machinery as a new layer of complexity in human telomerase activity. In this review we will discuss how AGO2 and other proteins which collaborate with AGO2 in RNAi pathway play a pivotal role in TERC stability and function
MicroRNAs: Novel regulators of immunity.
No full textMicroRNAs (miRNAs) are a growing class of evolutionarily conserved small non-coding RNAs that act as key regulators of gene expression at post-transcriptional level by targeting mRNAs for translational repression or degradation. These tiny regulators of gene expression have been shown to have unique tissue-specific, developmental stage-specific and disease-specific patterns. These observations suggest that miRNAs might be essential players in cell differentiation and maintenance of tissue type identity. Indeed, during the last years several studies highlighted that miRNAs play a critical role in the differentiation and function of the adaptive and innate immune systems. This review provides an overview of the miRNAs mode of action and of the important and diverse roles of miRNAs in regulating the development of hematopoietic system and in modulating immune responses. The implications arising in the field of autoimmune diseases will be discussed
Protein kinase C modulates light responses in Neurospora by regulating the blue light photoreceptor WC-1
No full textThe Neurospora protein kinase C (NPKC) is a regulator of light responsive genes. We have studied the function of NPKC in light response by investigating its biochemical and functional interaction with the blue light photoreceptor white-collar 1 (WC-1), showing that activation of NPKC leads to a significant decrease in WC-1 protein levels. Furthermore, we show that WC-1 and NPKC interact in a light-regulated manner in vivo, and that protein kinase C (PKC) phosphorylates WC-1 in vitro. We designed dominant negative and constitutively active forms of PKC which are able to induce either a large increase of WC-1 protein level or a strong reduction respectively. Moreover, these changes in PKC activity result in an altered light response. As WC-1 is a key component of Neurospora circadian clock and regulates the clock oscillator component FRQ we investigated the effect of NPKC-mutated forms on FRQ levels. We show that changes in PKC activity affect FRQ levels and the robustness of the circadian clock. Together these data identify NPKC as a novel component of the Neurospora light signal transduction pathway that modulates the circadian clock
Microarray dataset of Jurkat cells following miR-93 over-expression
Full text linkThe dataset presented here represents a microarray experiment of Jurkat cell line over-expressing miR-93 after lentiviral transgenic construct transduction. Three biological replicates have been performed. We further provide normalized and processed data, log2 Fold Change based ranked list and GOterms resulting table. The raw microarray data are available in the ArrayExpress database (www.ebi.ac.uk/arrayexpress) under accession number ArrayExpress: E-MTAB-4588
ARGONAUTE2 cooperates with SWI/SNF complex to determine nucleosome occupancy at human Transcription Start Sites.
Full text linkArgonaute (AGO) proteins have a well-established role in post-transcriptional regulation of gene expression as key component of the RNA silencing pathways. Recent evidence involves AGO proteins in mammalian nuclear processes such as transcription and splicing, though the mechanistic aspects of AGO nuclear functions remain largely elusive. Here, by SILAC-based interaction proteomics, we identify the chromatin-remodelling complex SWI/SNF as a novel AGO2 interactor in human cells. Moreover, we show that nuclear AGO2 is loaded with a novel class of Dicer-dependent short RNAs (sRNAs), that we called swiRNAs, which map nearby the Transcription Start Sites (TSSs) bound by SWI/SNF. The knock-down of AGO2 decreases nucleosome occupancy at the first nucleosome located downstream of TSSs in a swiRNA-dependent manner. Our findings indicate that in human cells AGO2 binds SWI/SNF and a novel class of sRNAs to establish nucleosome occupancy on target TSSs
microRNA-181a enhances cell proliferation in Acute Lymphoblastic Leukemia by targeting EGR1
No full textAcute Lymphoblastic Leukemia (ALL) is an aggressive cancer that occurs in both children and adults. Starting from an integrated analysis of miRNA/mRNA expression profiles in 20 ALL patients, we identify a negative correlation between miR-181a and EGR1. Coherently, miR-181a over-expression in Jurkat T-ALL cells decreases EGR1 expression, increasing cell proliferation and enhancing the cell-cycle progression from G1 to S phase. We show that EGR1 is a new direct target of miR-181a. Our findings suggest that miR-181a behaves as an onco-miRNA in ALL by down-regulating EGR1
The Expression of Vasoactive Intestinal Peptide Receptor 1 Is Negatively Modulated by MicroRNA 525-5p
No full textBackground: The human Vasoactive Intestinal Peptide (VIP) is a neurokine with effects on the immune system where it is involved in promoting tolerance. In this context, one of its receptors, VPAC1, has been found to be down-modulated in cells of the immune network in response to activating stimuli. In particular, the bacterial liposaccaride (LPS), a strong activator of the innate immune system, induces a rapid decrease of VPAC1 expression in monocytes and this event correlates with polymorphisms in the 3'-UTR of the gene. Methodology/Principal Findings: MicroRNA 525-5p, having as putative target the 3'-UTR region of VPAC1, has been analysed for its expression in monocytes and for its role in down-modulating VPAC1 expression. We report here that miR-525-5p is promptly up-regulated in LPS-treated monocytes. This microRNA, when co-transfected in 293T cells together with a construct containing the 3'-UTR of the VPAC1 gene, significantly reduced the luciferase activity in a standard expression assay. The U937 cell line as well as primary monocytes enforced to express miR-525-5p, both down-modulate VPAC1 expression at similar extent. Conclusions/Significance: Our results show that the response to an inflammatory stimulus elicits in monocytes a rapid increase of miR-525-5p that targets a signaling pathway involved in the control of the immune homeostasis
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