3,435 research outputs found

    Role of Sam68 in post-transcriptional gene regulation

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    The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation

    Post-transcriptional gene regulation in chondrocytes

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    Abstract The control of gene expression in articular chondrocytes is an essential factor in maintaining the homoeostasis of extracellular matrix synthesis and turnover necessary in healthy articular cartilage. Although much is known of how steady-state levels of gene expression and rates of transcription are altered, there has been a poorer understanding of gene control at the post-transcriptional level and its relevance to cartilage health and disease. Now, an emerging picture is developing of the importance of this tier of gene regulation, driven by in vitro studies and mouse genetic models. This level of cellular regulation represents an as yet unexplored area of potential intervention for the treatment of degenerative cartilage disorders such as osteoarthritis

    Principles and effects of microRNA-mediated post-transcriptional gene regulation

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    MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome. © 2006 Nature Publishing Group. All rights reserved

    Post-transcriptional gene regulation: From genome-wide studies to principles

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    Abstract.: Post-transcriptional regulation of gene expression plays important roles in diverse cellular processes such as development, metabolism and cancer progression. Whereas many classical studies explored the mechanistics and physiological impact on specific mRNA substrates, the recent development of genome-wide analysis tools enables the study of post-transcriptional gene regulation on a global scale. Importantly, these studies revealed distinct programs of RNA regulation, suggesting a complex and versatile post-transcriptional regulatory network. This network is controlled by specific RNA-binding proteins and/or non-coding RNAs, which bind to specific sequence or structural elements in the RNAs and thereby regulate subsets of mRNAs that partly encode functionally related proteins. It will be a future challenge to link the spectra of targets for RNA-binding proteins to post-transcriptional regulatory programs and to reveal its physiological implication

    Post-transcriptional gene regulation: From genome-wide studies to principles

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    Post-transcriptional regulation of gene expression plays important roles in diverse cellular processes such as development, metabolism and cancer progression. Whereas many classical studies explored the mechanistics and physiological impact on specific mRNA substrates, the recent development of genome-wide analysis tools enables the study of post-transcriptional gene regulation on a global scale. Importantly, these studies revealed distinct programs of RNA regulation, suggesting a complex and versatile post-transcriptional regulatory network. This network is controlled by specific RNA-binding proteins and/or non-coding RNAs, which bind to specific sequence or structural elements in the RNAs and thereby regulate subsets of mRNAs that partly encode functionally related proteins. It will be a future challenge to link the spectra of targets for RNA-binding proteins to post-transcriptional regulatory programs and to reveal its physiological implications

    Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA.

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    Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA (lncRNA), a heterogeneous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA (miRNA) pathways. lncRNA has been shown to act as both a source and an inhibitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying complexes by directing them to specific loci

    ELAV mediates 3' UTR extension in the Drosophila nervous system

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    Post-transcriptional gene regulation is prevalent in the nervous system, where multiple tiers of regulatory complexity contributeto the development and function of highly specialized cell types. Whole-genome studies in Drosophila have identified several hundred genes containing long 3′ extensions in neural tissues. We show that ELAV (embryonic-lethalabnormal visual system) is a key mediator of these neural-specific extensions. Misexpression of ELAV results in the ectopicsynthesis of long messenger RNAs (mRNAs) in transgenic embryos. RNA immunoprecipitation assays suggest that ELAV directlybinds the proximal polyadenylation signals of many target mRNAs. Finally, ELAV is sufficient to suppress 3′ end formationat a strong polyadenylation signal when tethered to a synthetic RNA. We propose that this mechanism for coordinating 3′ UTRextension may be generally used in a variety of cellular processes

    Investigation of the argonaute protein variants in Toxoplasma gondii and the contribution of argonaute to RNA silencing

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    Argonaute protein is a vital component in the RNA interference pathway and post-transcriptional gene regulation in eukaryotes and the protein was recently identified in Toxoplasma gondii. However, the molecular mechanism by which the argonaute protein participates in regulating gene regulation pathways is unclear. This study was aimed to investigate the presence of argonaute protein variants in T. gondii (TgAgo), and its contribution in post-transcriptional gene silencing pathway. Furthermore, the study was designed to elucidate the influence of TgAgo on parasite growth and bradyzoite development. Using PCR analysis, I did not detect any transcript variants of TgAgo. A single transcript of TgAgo was identified to have 2,232 nucleotides encompassing 5 exons. Protein immunoblot assay showed a single protein of ~58.5 kDa. Gene silencing assays demonstrated that knockout of argonaute expression (AGOKO) reduced the gene silencing ability of an RNAi-like mechanisms in T. gondii, suggesting the importance of TgAgo in post transcriptional gene regulation pathways. T. gondii growth pattern was unaffected by the removal of Ago expression. However, bradyzoite formation was increased in AGOKO strains. The study suggests that TgAgo is a vital component of bradyzoite formation in the life cycle of T. gondii

    Post‐transcriptional gene regulation by the exoribonuclease Pacman

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    The gene pacman (pcm) in Drosophila melanogaster encodes the exoribonuclease XRN1, which is highly conserved across eukaryotes and is the only known cytoplasmic exoribonuclease that degrades RNA in the 5’ – 3’ direction. Hypomorphic mutations to pacman have previously been shown cause developmental phenotypes, particularly during wing and thorax development. The focus of this thesis was twofold. Firstly, to create a null pacman allele and associated control lines to further characterise the phenotypes of pcm. Two new alleles were created, one of which was amorphic (pcm14). pcm14 is 100% lethal, and flies die during pupation. The wing imaginal discs of pcm14 larvae are less than half the size of those in wild‐type larvae at the same stage (3rd instar). It was also found that wing imaginal discs in the hypomorphic mutant pcm5 are significantly smaller than wild‐type, by almost 20%. Therefore, pcm appears to play a role in cell proliferation or apoptosis during the growth of wing imaginal discs. Along with pcm14, a new deficiency that includes pcm was created using a DrosDel Rearrangement Screen. The 17,963bp Df(1)ED7452 deficiency is >13 times smaller than the two other publically available deficiencies that include pcm
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