| 1. |
- Mattick, J. S., et al.
(författare)
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Long non-coding RNAs: definitions, functions, challenges and recommendations
- 2023
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Ingår i: Nature Reviews Molecular Cell Biology. - : Springer Science and Business Media LLC. - 1471-0072 .- 1471-0080. ; 24:6, s. 430-447
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Athie, Alejandro, et al.
(författare)
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Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion
- 2020
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 219:9
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is characterized by genomic instability leading to deletion or amplification of oncogenes or tumor suppressors. However, most of the altered regions are devoid of known cancer drivers. Here, we identify lncRNAs frequently lost or amplified in cancer. Among them, we found amplified lncRNA associated with lung cancer-1 (ALAL-1) as frequently amplified in lung adenocarcinomas. ALAL-1 is also overexpressed in additional tumor types, such as lung squamous carcinoma. The RNA product of ALAL-1 is able to promote the proliferation and tumorigenicity of lung cancer cells. ALAL-1 is a TNFα- and NF-κB-induced cytoplasmic lncRNA that specifically interacts with SART3, regulating the subcellular localization of the protein deubiquitinase USP4 and, in turn, its function in the cell. Interestingly, ALAL-1 expression inversely correlates with the immune infiltration of lung squamous tumors, while tumors with ALAL-1 amplification show lower infiltration of several types of immune cells. We have thus unveiled a pro-oncogenic lncRNA that mediates cancer immune evasion, pointing to a new target for immune potentiation.
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| 3. |
- Balick, B., et al.
(författare)
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pPNe: Lobe-Shaping Models & HST Images
- 2014
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Ingår i: Asymmetrical Planetary Nebulae VI conference, Proceedings of the conference held 4-8 November, 2013. ; , s. 4-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- HST images of some 50 pre planetary nebulae ("pPNe") are now available. A confrontation of images with theoretical shaping models is timely in order to determine whether one of the paradigms emerges as a best fit. The near-nuclear morphologies of twelve HST images of symmetric, bright, and well-resolved pPNe are compared to predictions of four basic types of simulations of collimated outflows. Diverging (or conical) outflows and magnetically launched winds generally provide a satisfactory morphological for the many pPNe whose lobes are edge brightened or open. Axial, or "cylindrical" flows (i.e., thin jets or clumps) nicely explain the formation of those lobes in pPNe with terminal bow shocks or spiral patterns inscribed on their edges. The review covers the past decade of HST imaging and related numerical modeling with an eye on future ALMA kinematic imaging.
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| 4. |
- Mitra, Sanhita, et al.
(författare)
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Subcellular distribution of p53 by the p53-responsive lncRNA NBAT1 determines chemotherapeutic response in neuroblastoma.
- 2021
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Ingår i: Cancer research. - 1538-7445. ; 81:6, s. 1457-1471
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma has a low mutation rate for the p53 gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation of wild-type p53. However, mechanisms leading to p53 inactivation via cytoplasmic accumulation are not well investigated. Here we show that the neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor NBAT1 is a p53-responsive lncRNA that regulates p53 subcellular levels. Low expression of NBAT1 provided resistance to genotoxic drugs by promoting p53 accumulation in cytoplasm and loss from mitochondrial and nuclear compartments. Depletion of NBAT1 altered CRM1 function and contributed to the loss of p53-dependent nuclear gene expression during genotoxic drug treatment. CRM1 inhibition rescued p53-dependent nuclear functions and sensitized NBAT1-depleted cells to genotoxic drugs. Combined inhibition of CRM1 and MDM2 was even more effective in sensitizing aggressive neuroblastoma cells with p53 cytoplasmic accumulation. Thus, our mechanistic studies uncover an NBAT1-dependent CRM1/MDM2-based potential combination therapy for high-risk neuroblastoma patients.
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| 5. |
- Sabin, L., et al.
(författare)
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ALMA reveals the coherence of the magnetic field geometry in OH 231.8+4.2
- 2020
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 495:4, s. 4297-4305
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Tidskriftsartikel (refereegranskat)abstract
- In a continuing effort to investigate the role of magnetic fields in evolved low- and intermediate-mass stars (principally regarding the shaping of their envelopes), we present new Atacama Large Millimeter/submillimeter Array (ALMA) high-resolution polarization data obtained for the nebula OH 231.8+4.2. We found that the polarized emission likely arises from aligned grains in the presence of magnetic fields rather than radiative alignment and self-scattering. The ALMA data show well organized electric field orientations in most of the nebula and the inferred magnetic field vectors (rotated by 90 degrees) trace an hourglass morphology centred on the central system of the nebula. One region in the southern part of OH 231.8+4.2 shows a less organized distribution probably due to the shocked environment. These findings, in conjunction with earlier investigations (maser studies and dust emission analysis at other scales and wavelengths) suggest an overall magnetic hourglass located inside a toroidal field. We propose the idea that the magnetic field structure is closely related to the architecture of a magnetic tower and that the outflows were therefore magnetically launched. While the current dynamical effect of the fields might be weak in the equatorial plane principally due to the evolution of the envelope, it would still be affecting the outflows. In that regard, the measurement of the magnetic field at the stellar surface, which is still missing, combined with a full magnetohydrodynamic treatment are required to better understand and constrain the events occurring in OH 231.8+4.2.
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| 6. |
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