| 1. |
- Mattick, J. S., et al.
(author)
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Long non-coding RNAs: definitions, functions, challenges and recommendations
- 2023
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In: Nature Reviews Molecular Cell Biology. - : Springer Science and Business Media LLC. - 1471-0072 .- 1471-0080. ; 24:6, s. 430-447
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Journal article (peer-reviewed)abstract
- Genes specifying long non-coding RNAs (lncRNAs) occupy a large fraction of the genomes of complex organisms. The term 'lncRNAs' encompasses RNA polymerase I (Pol I), Pol II and Pol III transcribed RNAs, and RNAs from processed introns. The various functions of lncRNAs and their many isoforms and interleaved relationships with other genes make lncRNA classification and annotation difficult. Most lncRNAs evolve more rapidly than protein-coding sequences, are cell type specific and regulate many aspects of cell differentiation and development and other physiological processes. Many lncRNAs associate with chromatin-modifying complexes, are transcribed from enhancers and nucleate phase separation of nuclear condensates and domains, indicating an intimate link between lncRNA expression and the spatial control of gene expression during development. lncRNAs also have important roles in the cytoplasm and beyond, including in the regulation of translation, metabolism and signalling. lncRNAs often have a modular structure and are rich in repeats, which are increasingly being shown to be relevant to their function. In this Consensus Statement, we address the definition and nomenclature of lncRNAs and their conservation, expression, phenotypic visibility, structure and functions. We also discuss research challenges and provide recommendations to advance the understanding of the roles of lncRNAs in development, cell biology and disease.
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| 3. |
- Zhou, A. X., et al.
(author)
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The long noncoding RNA TUNAR modulates Wnt signaling and regulates human β-cell proliferation
- 2021
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 320:4
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Journal article (peer-reviewed)abstract
- Many long noncoding RNAs (lncRNAs) are enriched in pancreatic islets and several lncRNAs are linked to type 2 diabetes (T2D). Although they have emerged as potential players in β-cell biology and T2D, little is known about their functions and mechanisms in human β-cells. We identified an islet-enriched lncRNA, TUNAR (TCL1 upstream neural differentiation-associated RNA), which was upregulated in β-cells of patients with T2D and promoted human β-cell proliferation via fine-tuning of the Wnt pathway. TUNAR was upregulated following Wnt agonism by a glycogen synthase kinase-3 (GSK3) inhibitor in human β-cells. Reciprocally, TUNAR repressed a Wnt antagonist Dickkopf-related protein 3 (DKK3) and stimulated Wnt pathway signaling. DKK3 was aberrantly expressed in β-cells of patients with T2D and displayed a synchronized regulatory pattern with TUNAR at the single cell level. Mechanistically, DKK3 expression was suppressed by the repressive histone modifier enhancer of zeste homolog 2 (EZH2). TUNAR interacted with EZH2 in β-cells and facilitated EZH2-mediated suppression of DKK3. These findings reveal a novel cell-specific epigenetic mechanism via islet-enriched lncRNA that fine-tunes the Wnt pathway and subsequently human β-cell proliferation.NEW & NOTEWORTHY The discovery that long noncoding RNA TUNAR regulates β-cell proliferation may be important in designing new treatments for diabetes.
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| 4. |
- Haghbayan, M. -H, et al.
(author)
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MapPro : Proactive runtime mapping for dynamic workloads by quantifying ripple effect of applications on networks-on-chip
- 2015
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In: Proceedings - 2015 9th IEEE/ACM International Symposium on Networks-on-Chip, NOCS 2015. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450333962
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Conference paper (peer-reviewed)abstract
- Increasing dynamic workloads running on NoC-based many-core systems necessitates efficient runtime mapping strategies. With an unpredictable nature of application profiles, selecting a rational region to map an incoming application is an NP-hard problem in view of minimizing congestion and maximizing performance. In this paper, we propose a proactive region selection strategy which prioritizes nodes that offer lower congestion and dispersion. Our proposed strategy, MapPro, quantitatively represents the propagated impact of spatial availability and dispersion on the network with every new mapped application. This allows us to identify a suitable region to accommodate an incoming application that results in minimal congestion and dispersion. We cluster the network into squares of different radii to suit applications of different sizes and proactively select a suitable square for a new application, eliminating the overhead caused with typical reactive mapping approaches. We evaluated our proposed strategy over different traffic patterns and observed gains of up to 41% in energy efficiency, 28% in congestion and 21% dispersion when compared to the state-of-the-art region selection methods. Copyright 2015 ACM.
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| 6. |
- Kanduri, A., et al.
(author)
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Dark silicon patterning : Efficient power utilization through run-time mapping
- 2017
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In: The Dark Side of Silicon. - Cham : Springer. - 9783319315966 - 9783319315942 ; , s. 237-258
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Book chapter (peer-reviewed)abstract
- An efficient run-time application mapping approach can considerably enhance resource utilization and mitigate the dark silicon phenomenon. In this chapter, we present a dark silicon aware run-time application mapping approach that patterns active cores alongside the inactive cores in order to evenly distribute power density across the chip. This approach leverages dark silicon to balance the temperature of active cores to provide higher power budget and better resource utilization, within a safe peak operating temperature. In contrast to exhaustive search based mapping techniques, the proposed agile heuristic approach has a negligible run-time overhead. This patterning strategy yields a surplus power budget of up to 17?% along with an improved throughput of up to 21?% in comparison with other state-of-the-art run-time mapping strategies, while the surplus budget is as high as 40?% compared to worst case scenarios.
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| 9. |
- Mondal, Tanmoy, 1981, et al.
(author)
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MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures
- 2015
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Journal article (peer-reviewed)abstract
- Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA–DNA triplex formation. We have found that RNA–DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA–DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.
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