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Regulation of the unfolded protein response by noncoding rna

AMERICAN JOUrnaL OF PHYSIOLOGY-CELL PHYSIOLOGY 2017年第3期313卷 C243-C254页

作者： McMahon, Mari Samali, Afshin Chevet, Eric Univ Rennes 1 INSERM Chem Oncogenesis Stress Signalling U1242 Rennes France Ctr Lutte Canc Eugene Marquis Rennes France Natl Univ Ireland Galway Sch Nat Sci Apoptosis Res Ctr Galway Ireland

Cells are exposed to various intrinsic and extrinsic stresses in both physiological and pathological conditions. To adapt to those conditions, cells have evolved various mechanisms to cope with the disturbances in protein demand, largely through the unfolded protein response (UPR) in the endoplasmic reticulum (ER), but also through the integrated stress response (ISR). Both responses initiate downstream signaling to transcription factors that, in turn, trigger adaptive programs and/or in the case of prolonged stress, cell death mechanisms. Recently, noncoding rnas, including microrna and long noncoding rna, have emerged as key players in the stress responses. These noncoding rnas act as both regulators and effectors of the UPR and fine-tune the output of the stress signaling pathways. Although much is known about the UPR and the cross talk that exists between pathways, the contribution of small noncoding rna has not been fully assessed. Herein we bring together and review the current known functions of noncoding rna in regulating adaptive pathways in both physiological and pathophysiological conditions, illustrating how they operate within the known UPR functions and contribute to diverse cellular outcomes.

关键词： endoplasmic noncoding rna proteostasis stress

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Crucial role of noncoding rna in driving prostate cancer development and progression

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EPIGENOMICS 2017年第1期9卷 1-3页

作者： Guo, Haiyang Ahmed, Musaddeque Hua, Junjie Soares, Fraser He, Housheng Hansen Univ Hlth Network Princess Margaret Canc Ctr Toronto ON Canada Univ Toronto Dept Med Biophys Toronto ON Canada

[...]lncrna CTBP1-AS directly suppresses CTBP1 transcription by guiding the PSF-HDAC-Sin3A complex to the CTBP1 promoter, which abolishes the androgen-mediated gene repression program (9). [...]we demonstrated that PCAT1 interacts with AR and LSD1, which mediates their occupancy at the enhancers of GNMT and DHCR24, two androgen late-response genes that participate in PCa development and progression. Since these data are becoming increasingly available for many cancer types, our pipeline will also be useful for the lncrna study in other cancer types. Many GWAS SNPs also locate in lncrna gene bodies (1). Since most lncrnas function through interaction with other molecules (such as rna, DNA and protein), some studies have revealed that those interactions have a sequence-specific pattern (15).

关键词： CRISPR noncoding rna prostate cancer risk SNP transcription

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Functional insights into long antisense noncoding rna Kcnq1ot1 mediated bidirectional silencing

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rna BIOLOGY 2008年第4期5卷 208-211页

作者： Kanduri, Chandrasekhar Uppsala Univ Dept Genet & Pathol Rudbeck Lab Uppsala 75185 Sweden

The prevailing view has been that noncoding aritisense rna primarily regulates the transcriptional activity of its sense counterpart, however, a subset of long noncoding antisense rnas, such as Kcnq1ot1 and Air, have been shown to regulate the transcriptional silencing of multiple genes spread over several hundred kilobases on either side of their promoters. It is however unknown how these long rnas regulate the transcriptional silencing of multiple genes. Our recent work demonstrated through exploiting an episomal-based system that the Kcnq1ot1 rna harbors a silencing domain at its 5' end which mediates transcriptional silencing through introducing repressive histone modifications, and by interacting with the chromatin and targeting the associated regions to the perinucleolar space. Based on our current findings as well as previous findings from other labs, we propose a model resembling that of Xist-mediated chromosomal silencing, wherein Kcnq1ot1 rna initiates transcriptional silencing by coating the flanking chromatin regions and directing the heterochromatin machinery. Maintenance of silencing through subsequent cell divisions would then occur via the targeting of Kcnq1ot1-associated chromatin to the perinucleolar space.

关键词： Kcnq1ot1 antisense rna chromatin noncoding rna epigenetics

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Advances in noncoding rna in children allergic rhinitis

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INTErnaTIONAL FORUM OF ALLERGY & RHINOLOGY 2024年第8期14卷 1350-1362页

作者： Li, Shuman Cui, Hongtao Lu, Huina Zheng, Shan Yuan, Chao Chongqing Med Univ Chongqing Peoples R China Chongqing Tradit Chinese Med Hosp Dept Pediat 6 Panxi Qizhi Rd Chongqing 400021 Peoples R China

Background: A chronic condition that significantly reduces a child's quality of life is allergic rhinitis (AR). The environment and allergens that the body is regularly exposed to can cause inflammatory and immunological reactions, which can change the expression of certain genes Epigenetic changes are closely linked to the onset and severity of allergy disorders according to mounting amounts of data. noncoding rnas (ncrnas) are a group of rna molecules that cannot be converted into polypeptides. The three main categories of ncrnas include micrornas (mirnas), long noncoding rnas (lncrnas), and circular rnas (circrnas). Ncrnas play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. Methods: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. Results: Recent findings indicate that various categories of ncrnas play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. Conclusion: This article demonstrates the significance and progress of ncrnas in children's AR. The database covers three key areas: mirnas, lncrnas, and circrnas. Additionally, potential avenues for future research to facilitate the practical application of ncrnas as therapeutic targets and biomarkers will be explore.

关键词： biomarkers children allergic rhinitis immunomodulatory noncoding rna

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Exosomes as Vehicles for noncoding rna in Modulating Inflammation: A Promising Regulatory Approach for Ischemic Stroke and Myocardial Infarction

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JOUrnaL OF INFLAMMATION RESEARCH 2024年 17卷 7485-7501页

作者： Lai, Zhuhong Ye, Tingqiao Zhang, Mingjun Mu, Ying Univ Elect Sci & Technol China Mianyang Cent Hosp Sch Med Dept Cardiol Mianyang 621000 Peoples R China

Exosomes have grown as promising carriers for noncoding rnas (ncrnas) in the treatment of inflammation, particularly in conditions like ischemic stroke and myocardial infarction. These ncrnas, which include micrornas (mirnas) and long noncoding rnas (lncrnas), play a crucial role in regulating inflammatory pathways, presenting new therapeutic opportunities. In both ischemic stroke and myocardial infarction, inflammation significantly influences disease progression and severity. Exosomes can deliver ncrnas directly to specific cells and tissues, providing a targeted approach to modulate gene expression and reduce inflammation. Their biocompatibility and low risk of inducing immune responses make exosomes ideal therapeutic vehicles. Ongoing research is focused on optimizing the loading of ncrnas into exosomes, ensuring efficient delivery, and understanding the mechanisms by which these ncrnas mitigate inflammation. In ischemic stroke, exosome-derived ncrnas originate from various cell types, including neurons, M2 microglia, patient serum, genetically engineered HEK293T cells, and mesenchymal stromal cells. In the case of myocardial infarction, these ncrnas are sourced from mesenchymal stem cells, endothelial cells, and patient plasma. These exosome-loaded ncrnas play a significant role in modulating inflammation in both ischemic stroke and myocardial infarction. As this research advances, therapies based on exosomes may completely change how diseases linked to inflammation are treated, offering new avenues for patient care and recovery. This review explores the latest advancements in understanding how exosomes impact specific inflammatory components, with a particular emphasis on the role of ncrnas contained in exosomes. The review concludes by highlighting the clinical potential of exosome-derived ncrnas as innovative therapeutic and diagnostic tools.

关键词： exosomes noncoding rna inflammation ischemic stroke myocardial infarction

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Aberrant expression of long noncoding rna TMEVPG1 in patients with primary immune thrombocytopenia

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AUTOIMMUNITY 2016年第7期49卷 496-502页

作者： Li, Huiyuan Hao, Yating Zhang, Donglei Fu, Rongfeng Liu, Wenjie Zhang, Xian Xue, Feng Yang, Renchi Chinese Acad Med Sci Inst Hematol & Blood Dis Hosp State Key Lab Expt Hematol 288 Nanjing Rd Tianjin 300020 Peoples R China Peking Union Med Coll 288 Nanjing Rd Tianjin 300020 Peoples R China

TMEVPG1 is a long noncoding rna, which can promote Interferon gamma (IFNG) transcript as an enhancer. It has been reported that plasma IFNG concentration was elevated and partly due to dysregulation of micro rnas in patients with primary immune thrombocytopenia (ITP). However, the effect of long noncoding rna on IFNG expression in ITP is currently not well understood. To explore whether TMEVPG1 is involved in ITP, this study examined the TMEVPG1 expression and analyzed the association between TMEVPG1 transcript and IFNG expression in patients with ITP and healthy controls. The result showed that TMEVPG1 expression in peripheral blood mononuclear cells (PBMCs) from active ITP patients were lower than in that of healthy controls. Further activation for 24 h in vitro resulted in decreased TMEVPG1 while elevated IFNG mrna and protein expressions in activated PBMCs compared with un-activated PBMCs both in ITP patients and healthy controls. However, TMEVPG1 and IFNG mrna had same up-regulated tendency after short-time activation (1, 2 and 4 h) in healthy controls. In addition, we detected T helper 1 (Th1) cell associated transcription factors T-bet, STAT1 and STAT4 mrna levels, and found T-bet mrna expression was lower in PBMCs from ITP patient in remission compared with healthy controls. In conclusion, we speculated that TMEVPG1 could promote IFNG transcription, and IFNG over-expression negative feedback regulated on TMEVPG1 expression, which resulted in decreased TMEVPG1 in ITP patients.

关键词： noncoding rna TMEVPG1 interferon gamma primary immune thrombocytopenia Th1

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Activity and roles of Arabidopsis thaliana XRN family exoribonucleases in noncoding rna pathways

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JOUrnaL OF PLANT RESEARCH 2017年第1期130卷 25-31页

作者： Kurihara, Yukio RIKEN Ctr Sustainable Resource Sci Synthet Genom Res Grp Tsurumi Ku 1-7-22 Suehiro Cho Yokohama Kanagawa 2300045 Japan

rna metabolism is mediated by several sophisticated exo- or endo- ribonucleases. XRN family proteins are the conserved 5'-3' exoribonucleases in eukaryotes. A. thaliana genome encodes three XRN homologs (AtXRN2, AtXRN3 and AtXRN4) and their independent or redundant roles, which are possibly plant-specific in some cases, have been reported. AtXRN2 acts in maturation of ribosomal rnas partially with AtXRN3. AtXRN3 is also involved in elimination of 3' remnants of microrna precursors and in termination of mrna transcription events. AtXRN4 degrades not only a small fraction of mrnas in stress response but also 3' cleavage products of mirna-mediated cleavage of target mrnas. Moreover, all AtXRNs are important factors to suppress unexpected rna silencing occurrence. Thus, this review summarizes and discusses multiple roles of AtXRN exoribonucleases and their relationship with noncoding rna pathways including rna silencing pathways.

关键词： XRN Exoribonuclease FIERY1 noncoding rna

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Identification of a novel noncoding rna gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest

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INTErnaTIONAL JOUrnaL OF CANCER 2007年第4期121卷 767-775页

作者： Yoon, Heejei He, Huiling Nagy, Rebecca Davuluri, Ramana Suster, Saul Schoenberg, Daniel Pellegata, Natalia de la Chapelle, Albert Ohio State Univ Human Canc Genet Program Ctr Comprehens Canc Tzagournis Res Facil 646 Columbus OH 43210 USA Ohio State Univ Dept Pathol Columbus OH 43210 USA Ohio State Univ Dept Mol & Cellular Biochem Columbus OH 43210 USA

In search of tumor suppressor genes in papillary thyroid carcinoma (PTC), we previously used gene expression profiling to identify genes underexpressed in tumor compared with paired unaffected tissue. While searching for loss of heterozygosity (LOH) in genomic regions harboring candidate tumor suppressor genes, we detected LOH in a similar to 20 kb region around marker D9S176. Several ESTs flanking D9S176 were underexpressed in PTC tumors, and for one of the ESTs, downregulation was highly associated with the activating BRAF mutation V600E, the most common genetic lesion in PTC. A novel gene, NAMA, (noncoding rna associated with MAP kinase pathway and growth arrest) containing the affected EST was cloned and characterized. NAMA is weakly expressed in several human tissues, and the spliced forms are primarily detected in testis. Several characteristics of NAMA suggest that it is a nonprotein coding but functional rna;it has no long open reading frames (ORFs);the exons exhibit low sequence identity in the evolutionarily conserved regions;it is inducible by knockdown of BRAF, inhibition of the MAP kinase pathway, growth arrest and DNA damage in cancer cell lines. We suggest that NAMA is a noncoding rna associated with growth arrest. (c) 2007 Wiley-Liss, Inc.

关键词： papillary thyroid carcinoma noncoding rna BRAF NAMA growth arrest

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SASP regulation by noncoding rna

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MECHANISMS OF AGEING AND DEVELOPMENT 2017年 168卷 37-43页

作者： Panda, Amaresh C. Abdelmohsen, Kotb Gorospe, Myriam NIA Lab Genet & Genom Intramural Res Program NIH Baltimore MD 21224 USA

noncoding rnas (ncrnas), including micro (mi)rnas, long noncoding (lnc)rnas, and circular (circ)rnas, control specific gene expression programs by regulating transcriptional, post-transcriptional, and post-translational processes. Through their broad influence on protein expression and function, ncrnas have been implicated in virtually all cellular processes such as proliferation, senescence, quiescence, differentiation, apoptosis, and the stress and immune responses. Senescence is a cellular phenotype associated with the physiologic decline of aging and with age-related pathologies. Besides their characteristic terminal growth arrest and differential gene expression programs, senescent cells are known to secrete potent pro-inflammatory, angiogenic, and tissue-remodeling factors. This important trait, known as the senescence-associated secretory phenotype (SASP), influences many biological processes such as tissue repair and regeneration, tumorigenesis, and the aging-associated pro-inflammatory state. Here, we review the micrornas, lncrnas, and circrnas that influence the production of SASP factors and discuss the rising interest in SASP-regulatory ncrnas as diagnostic and therapeutic targets.

关键词： Transcriptome Post-transcriptional gene regulation noncoding rna Long noncoding rna microrna mrna stability mrna translation Ribonucleoprotein complexes Transcriptional gene regulation Aging Inflammatory cytokines Senescence

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Auto-assembly as a new regulatory mechanism of noncoding rna

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CELL CYCLE 2009年第6期8卷 952-954页

作者： Busi, Florent Cayrol, Bastien Lavelle, Christophe LeDerout, Jacques Pietrement, Olivier Le Cam, Eric Geinguenaud, Frederic Lacoste, Jerome Regnier, Philippe Arluison, Veronique CNRS IBPC UPR 9073 F-75005 Paris France Univ Paris Diderot Paris France Univ Paris Diderot Paris 7 Unit Funct & Adapt Biol BFA CNRS Lab Mol & Cellular Responses Xenobiot Paris France Univ Illinois Dept Phys Urbana IL 61801 USA Inst Cancerol Gustave Roussy Lab Microscopie Mol & Cellulaire CNRS UMR 8126 Villejuif France Univ Paris 11 Villejuif France Univ Paris 13 UFR SMBH UMR 7033 CNRSBioMoCeTi Bobigny France Univ Paris 06 Paris France CNRS FRE 3231 Lab Jean Perrin F-75005 Paris France

An abstract is not available for this article.

关键词： noncoding rna srna macromolecule self-assembly GcvB translational control riboregulation

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