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PI3K/AKT signaling mediates stress-inducible amyloid formation through c-Myc

Cell Reports 2025年第5期44卷

作者： Lacroix, Emma Momchilova, Evgenia A. Chandhok, Sahil Padavu, Mythili Zapf, Richard Audas, Timothy E. Department of Molecular Biology and Biochemistry Simon Fraser University 8888 University Drive Burnaby V5A 1S6 BC Canada Centre for Cell Biology Development and Disease Simon Fraser University 8888 University Drive Burnaby V5A 1S6 BC Canada

In response to environmental stress, eukaryotic cells reversibly form functional amyloid aggregates called amyloid bodies (A-bodies). While these solid-like biomolecular condensates share many biophysical characteristics with pathological amyloids, A-bodies are non-toxic, and they induce a protective state of cellular dormancy. As a recently identified structure, the modulators of A-body biogenesis remain uncharacterized, with the seeding noncoding rna being the only known regulatory factor. Here, we use an image-based high-throughput screening approach to identify candidate pathways regulating A-body biogenesis. Our data demonstrate that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling axis meditates A-body formation during stress exposure, with AKT activation repressing glycogen synthase kinase-3 (GSK3)-mediated degradation of c-Myc. This enhances c-Myc binding to regulatory elements of the seeding noncoding rna, upregulating the transcripts that nucleate A-body formation. Identifying a link between PI3K/AKT signaling, c-Myc, and physiological amyloid aggregates extends the range of activity for these well-established regulators while providing insight into cellular components whose dysregulation could underly amyloidogenic disorders. © 2025 The Author(s)

关键词： Akt amyloids biomolecular condensates c-Myc CP: Cell biology CP: Neuroscience environmental stress heat shock noncoding rna nucleolus PI3K signal transduction

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Signals from noncoding rnas: Unconventional roles for conventional pol III transcripts

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INTErnaTIONAL JOUrnaL OF BIOCHEMISTRY & CELL BIOLOGY 2012年第11期44卷 1847-1851页

作者： Hu, Shanshan Wu, Jing Chen, Liang Shan, Ge Univ Sci & Technol China Sch Life Sci Hefei 230027 Anhui Peoples R China Huazhong Univ Sci & Technol Sch Life Sci & Technol Wuhan 430074 Hubei Province Peoples R China

A range of noncoding rnas are transcribed by pol III. A lot of them such as trna, 7SL rna, 7SK rna, 5S rna, MRP rna, Y rnas, Hi rna, and vault rnas are considered as "house keeping" rnas essential for eukaryotic cells. In recent years, researchers started to recognize the existence of unconventional functions of many pol III transcripts other than classical "house keeping" roles. Therefore, these ncrnas could now be viewed as molecules with functional regulatory signals as well as cellular building blocks. These noncoding rnas, all transcribed by pol III, may assemble regulatory networks with analogy to signaling pathways in eukaryotic cells. In this review we discuss these unconventional roles of pol III transcripts. (C) 2012 Elsevier Ltd. All rights reserved.

关键词： Pol III noncoding rna trna 5S rrna 7SL rna

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Long noncoding rnas. Molecular switch and therapeutic target molecules of disease processes

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NEPHROLOGE 2017年第1期12卷 59-61页

作者： Lorenzen, J. M. Univ Spital Zurich Ramistr 100 CH-8091 Zurich Switzerland

Long noncoding rnas (lncrna) are regulatory rna species, which have recently come into the focus of scientific interest. Until now little was known about their mode of action, although according to many studies it was presumed that they exercise an important epigenetic function within cells under physiological conditions as well as in disease processes. This article presents some of these regulatory functions and the suggested classification due to the localization as well as the current functional classification of lncrnas. Several lncrnas have now been identified that are important within the framework of renal and cardiovascular diseases. On the basis of the most recent resarch results, this article demonstrates how novel therapeutic routes for these diseases can be pursued in the future using lncrna antagonists or viral constructs on overexpression.

关键词： noncoding rna Epigenetics Kidney diseases Cardiovascular diseases Therapeutics

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Regulatory noncoding rnas: functions and applications in health and disease

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FEBS JOUrnaL 2021年第22期288卷 6308-6309页

作者： Arraiano, Cecilia Maria Univ Nova Lisboa Inst Tecnol Quim & Biol Antonio Xavier Av Republ P-2780157 Oeiras Portugal

Science is facing a new rna world that is shaping our knowledge, and we are discovering a new horizon in molecular biology. New technologies revealed thousands and thousands of new rnas, most of them located in what was once known as the "dark matter of DNA". They are functional regulatory rnas and do not code for proteins, and they orchestrate the cellular function according to the changes needed. These noncoding rnas are ubiquitous, and they are present from viruses to humans. In this Virtual Issue, The FEBS Journal features a collection of recent articles on long noncoding rnas, micrornas, and circular rnas. It gives a broad perspective regarding their role in vascular diseases, ocular diseases, immune cell development and homeostasis, inflammation, production of extracellular matrix, and cancer. Furthermore, review-type articles highlight the potential use of noncoding rnas in a wide range of applications.

关键词： circrna disease functional rna gene expression lncrna microrna noncoding rna regulatory rna

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An expanding universe of noncoding rnas between the poles of basic science and clinical investigations

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EPIGENOMICS 2016年第3期8卷 317-319页

作者： Weil, Patrick P. Hensel, Kai O. Weber, David Postberg, Jan Univ Witten Herdecke HELIOS Med Ctr Wuppertal Ctr Clin & Translat Res Ctr Biomed Educ & Res ZBAFFac Hlth Heusnerstr 40 D-42283 Wuppertal Germany

Since the discovery of rnai, great efforts have been undertaken to unleash the potential biomedical applicability of small noncoding rnas, mainly mirnas, involving their use as biomarkers for personalized diagnostics or their usability as active agents or therapy targets. The research's focus on the noncoding rna world is now slowly moving from a phase of basic discoveries into a new phase, where every single molecule out of many hundreds of cataloged noncoding rnas becomes dissected in order to investigate these molecules' biomedical relevance. In addition, rna classes neglected before, such as long noncoding rnas or circular rnas attract more attention. Numerous timely results and hypotheses were presented at the 2015 Keystone Symposium 'Micrornas and noncoding rnas in Cancer'.

关键词： biomarkers cancer long noncoding rna microrna noncoding rna rna interference

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Identifying Long noncoding rnas and Examining Their Functional Roles in Brassicaceae

Identifying Long Noncoding RNAs and Examining Their Function...

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作者： Palos, Kyle The University of Arizona

学位级别：Ph.D., Doctor of Philosophy

Tremendous progress has been made over the last century characterizing the structure, function, and evolutionary dynamics of protein-coding genes. Over the last three decades, biologists have sequenced the genomes of a variety of organisms, and it quickly became apparent that a relatively small portion of most genomes encode protein-coding genes. We now know that the non-protein-coding space contains repetitive sequences along with non-coding rnas. Many of these non-coding rnas encode housekeeping transcripts such as: ribosomal rnas, transfer rnas, small nucleolar rnas, and small nuclear rnas. However, the remaining transcripts include regulatory rnas that have become the focus of intense investigation over the past two decades. These include the micrornas and the small interfering rnas which both act to knock down gene expression. More recently, a class of transcripts called long non-coding rnas (lncrnas) have been interrogated. One well described, functional lncrna is the telomerase rna which is necessary for genome stability via the maintenance of chromosome ends following DNA replication (Dew-Budd et al. 2020). While lncrnas have been known for more than two decades, their functions have remained enigmatic; there are few functionally characterized lncrnas. However, lncrnas that have been characterized, especially in mammalian systems, appear to fine tune a plethora of developmental and regulatory processes, along with responses to environmental cues. Lncrnas are frequently expressed at low levels and in specific tissues; they are often poorly conserved among closely related species (Palos et al. 2021). As high-throughput rna-sequencing becomes more widely available and used, researchers have employed the resulting data to identify lncrnas en masse. For mammals, a variety of high-quality resources have been used to generate informative annotations to allow for improved hypothesis generation. These resources include GENCODE (Frankish et al. 2021), coupled with lnc

关键词： Computational biology noncoding rna Stress biology

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The evolution of noncoding rnas in the Drosophila melanogaster genome

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Biophysics (Russian Federation) 2015年第5期60卷 745-751页

作者： Juravleva, E.V. Mironov, A.A. Department of Bioengineering and Bioinformatics Moscow State University Moscow 119234 Russian Federation Kharkevich Institute of Information Transmission Problems Russian Academy of Sciences Bol’shoi Karetnyi per. 19/1 Moscow 127051 Russian Federation

noncoding rnas (ncrnas) are important regulatory molecules that function owing to their specific secondary structures. The secondary structure depends on the rna sequence and can be viewed as a combination of loops, stems, and pseudoknot regions. Each local rna part, as well as the entire molecule, tends to achieve the minimal free energy by assuming a certain structure. New mutations may change the free energy of the current rna structure so that another structure becomes optimal, thus altering the rna function. The chance that a mutation will cause structural alterations depends on the mutation position in the rna secondary structure. Divergence estimates have been found to differ between paired and unpaired regions, the difference arises because selection is aimed at preserving the ncrna secondary structure. A more detailed analysis of the evolutionary differences between loops and stems in all of the most important ncrna classes may be of interest for developing the algorithms to search a genome for ncrna genes. This study focused on natural selection acting on the loop and stem regions in five ncrna classes. An attempt was made to associate selection characteristics with changes in free energy. The Drosophila melanogaster genome was used as a model. © 2015, Pleiades Publishing, Inc.

关键词： evolution of noncoding rna noncoding rna rna secondary structure

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Long noncoding rnas in the initiation, progression, and metastasis of hepatocellular carcinoma

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Non-coding rna Research 2017年第3-4期2卷 129-136页

作者： DiStefano, Johanna K. Program in Epigenetics and Fibrosis Translational Genomics Research Institute 445 N 5th Street Phoenix 85004 AZ United States

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite awareness of risk factors for the development of HCC and advances in the diagnosis and clinical management of the disease, the molecular mechanisms underlying hepatocarcinogenesis remain poorly understood. Recent experimental studies provide strong evidence that long noncoding rnas (lncrnas), non-protein-coding transcripts with lengths >200 basepairs, contribute to the pathogenesis of numerous human diseases. Over the past decade, a role for lncrnas in the initiation, progression, and metastasis of HCC has likewise emerged and developed into a highly active area of research. Although many lncrnas appear to be dysregulated in HCC, extensive functional characterization has been performed on only a small proportion of these candidates to date. This review summarizes select lncrnas that have been shown to wield functional relevance in the initiation, progression, or metastasis of HCC, focusing on the specific mechanisms by which lncrna effects might be linked to clinical manifestations of the disease. In addition, an overview of circulating lncrnas that have been identified as potential biomarkers for the diagnosis and prognosis of HCC is provided. © 2017 The Author

关键词： Hepatocellular carcinoma HOTAIR HULC lncrnas Long noncoding rnas noncoding rna

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Epigenetic regulations of chromatin dynamics: A role of noncoding rnas in epigenetic activation of Drosophila Hox genes

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International Congress Series 2007年 1299卷 239-241页

作者： Nishioka, Kenichi Hirose, Susumu Department of Developmental Genetics National Institute of Genetics Mishima Shizuoka 411-8540 1111 Yata Japan

The Hox genes are well-studied genes which are regulated by an epigenetic mechanism. Accumulated evidence suggests that DNA methylation and histone modifications have a crucial function to regulate them. Here we try to investigate whether noncoding rnas derived from cis-regulatory elements within the Drosophila Abd-B locus are required for proper expression of the target gene. First we analyzed expression patterns of the noncoding rnas during embryonic stages by in situ hybridizations. We found that they are spatially controlled and are shown co-linear pattern with their genomic organization. We also found that the noncoding rnas are strictly localized in the nucleus. We speculate that there is a novel epigenetic activation mechanism by noncoding rnas. © 2006 Elsevier B.V. All rights reserved.

关键词： Chromatin Drosophila Epigenetics noncoding rna

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noncoding rnas in Cancer Development

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Cancer Biology 1000年第1期1卷 163-184页

作者： Chao-Po Lin Lin He Division of Cellular and Developmental Biology Department of Molecular and Cell Biology University of California Berkeley California 94705 email: lhe@berkeley.edu

It is becoming increasingly clear that a large repertoire of noncoding rnas (ncrnas) are actively transcribed from the mammalian genome, regulating diverse cellular processes in development and diseases through a variety of gene regulatory mechanisms. As the most extensively studied ncrna species, micrornas (mirnas) are important components in the oncogene and tumor suppressor network, and have been employed as potential biomarkers, therapeutic reagents, and therapeutic targets for cancer treatment. Other ncrnas, particularly long noncoding rnas, also have a profound impact on cancer development, as demonstrated in both mouse and human tumor models. We are only starting to understand the realm of ncrna biology, and the exact molecular mechanisms governing ncrna functions remain largely unexplored. With numerous ncrnas discovered through high-throughput approaches, understanding their functions in malignant transformation will be one of the most exciting challenges in cancer research.

关键词： noncoding rna microrna long noncoding rna cancer

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