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The dichotomy of p53 regulation by noncoding rnas

Journal of Molecular Cell Biology 2014年第3期8卷 198-205页

作者： Qipan Deng Lindsey Becker Xiaodong Ma Xiaoming Zhong Ken Young Kenneth Ramos and Yong Li Department of Biochemistry and Molecular Biology School of Medicine University of Louisville 319 Abraham Flexner Way Louisville KY 40202 USA Department of Cardiology Huaihe Hospital of Henan University Kaifeng 475000 China Department of Hematopathology The University of Texas MD AndersonCancer Center Houston TX 77030 USA School of Life Science and Technology ShanghaiTech University Shanghai 200031 Cl~ina

The p53 tumor suppressor gene is the most frequently mutated gene in cancer. Significant progress has been made to discern the im- portance of p53 in coordinating cellular responses to DNA damage, oncogene activation, and other stresses. noncoding rnas are rna molecules functioning without being translated into proteins. In this work, we discuss the dichotomy of p53 regulation by noncoding rnas with four unconventional questions. First, is overexpression of micrornas responsible for p53 inactivation in the absence of p53 mutation？ Second, are there somatic mutations in the noncoding regions of the p53 gene？ Third, is there a germline mutant in the non- coding regions of the p53 gene that predisposes carriers to cancer？ Fourth, can p53 activation mediated by a noncoding rna mutation cause cancer？ This work highUghts the prominence of noncoding rnas in p53 dysregutation and tumorigenesis.

关键词： noncoding rna p53 activation mutation 3＇UTR poiymorphism ribosomopathies

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Androgen-dependent and DNA-binding-independent association of androgen receptor with chromatic regions coding androgen-induced noncoding rnas

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BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 2021年第10期85卷 2121-2130页

作者： Sawada, Takahiro Nishimura, Koichi Mori, Jinichi Kanemoto, Yoshiaki Kouzmenko, Alexander Amano, Rei Hayakawa, Akira Tokiwa, Suguru Shimmura, Hiroaki Kato, Shigeaki Tokiwa Fdn Res Inst Innovat Med Iwaki Fukushima Japan Iryo Sosei Univ Grad Sch Life Sci & Engn Iwaki Fukushima Japan Jyoban Hosp Tokiwa Fdn Dept Hematol Iwaki Fukushima Japan Jyoban Hosp Tokiwa Fdn Dept Urol Iwaki Fukushima Japan Fukushima Med Univ Sch Med Fukushima Fukushima Japan Tokushima Univ Fujii Mem Inst Med Sci Inst Adv Med Sci Inst Biomed Sci Tokushima Japan

Androgen induces the binding of its receptor (AR) to androgen-responsive elements (AREs), while genome-wide studies showed that most androgen-induced AR binding sites on chromatin were unrelated to AREs. Enhancer rnas (erna5), a class of noncoding rnas (ncrnas), are transcribed from superenhancers (SEs) and trigger the formation of large ribonucleoprotein condensates of transcription factors. By in silico search, an SE is found to be located on the locus of KLK3 that encodes prostate specific antigen. On the KLK3 SE, androgen-induced expression of ncrnas was detected and designated as KLK3ernas in LNCaP cells, and androgen-induced association of AR and FOXA1 on the KLK3erna coding regions was detected. Such androgen-induced association of an AR mutant lacking DNA binding activity on the KLK3erna coding regions was undetectable on an exogenous ARE. Thus, the present findings suggest a molecular basis of androgen-induced association of AR with chromatin on ARE-unrelated sequences. [GRAPHICS] .

关键词： androgen receptor noncoding rna enhancer rna liquid-liquid phase separation (LLPS) ribonucleoprotein (RNP)

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Rapid and high-throughput construction of microbial cell-factories with regulatory noncoding rnas

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BIOTECHNOLOGY ADVANCES 2015年第6期33卷 914-930页

作者： Chaudhary, Amit Kumar Na, Dokyun Lee, Eun Yeol Kyung Hee Univ Dept Chem Engn Gyeonggi Do 446701 South Korea Chung Ang Univ Sch Integrat Engn Seoul 156756 South Korea

Due to global crises such as pollution and depletion of fossil fuels, sustainable technologies based on microbial cell-factories have been garnering great interest as an alternative to chemical factories. The development of microbial cell-factories is imperative in cutting down the overall manufacturing cost. Thus, diverse metabolic engineering strategies and engineering tools have been established to obtain a preferred genotype and phenotype displaying superior productivity. However, these tools are limited to only a handful of genes with permanent modification of a genome and significant labor costs, and this is one of the bottlenecks associated with biofactory construction. Therefore, a groundbreaking rapid and high-throughput engineering tool is needed for efficient construction of microbial cell-factories. During the last decade, copious small noncoding rnas (ncrnas) have been discovered in bacteria. These are involved in substantial regulatory roles like transcriptional and post-transcriptional gene regulation by modulating mrna elongation, stability, or translational efficiency. Because of their vulnerability, ncrnas can be used as another layer of conditional control over gene expression without modifying chromosomal sequences, and hence would be a promising high-throughput tool for metabolic engineering. Here, we review successful design principles and applications of ncrnas for high-throughput metabolic engineering or physiological studies of diverse industrially important microorganisms. (C) 2015 Elsevier Inc. All rights reserved.

关键词： noncoding rna Synthetic rna Microbial factory Gene silencing High-throughput Metabolic engineering Synthetic biology Small regulatory rna

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noncoding rnas in the regulation of DNA replication

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TRENDS IN BIOCHEMICAL SCIENCES 2014年第8期39卷 341-343页

作者： Ge, Xin Quan Lin, Haifan Yale Univ Sch Med Yale Stem Cell Ctr New Haven CT 06520 USA Yale Univ Sch Med Dept Cell Biol New Haven CT 06520 USA

noncoding rnas (ncrnas) have crucial roles in epigenetic, transcriptional, and post-transcriptional regulation. Recent studies have begun to reveal a role of ncrnas in DNA replication. Here, we review the roles of ncrnas in regulating different aspects of DNA replication in prokaryotic and eukaryotic systems. We speculate that ncrnas might function to guide the origin recognition complex (ORC) to chromosomal DNA during replication initiation in higher eukaryotes.

关键词： noncoding rna DNA replication mirna ORC primer

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Regulatory noncoding rnas at Hox loci

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BIOCHEMISTRY AND CELL BIOLOGY 2009年第1期87卷 27-34页

作者： Brock, Hugh W. Hodgson, Jacob W. Petruk, Svetlana Mazo, Alexander Univ British Columbia Inst Life Sci Mol Epigenet Grp Vancouver BC V6T 1Z3 Canada Thomas Jefferson Univ Dept Biochem & Mol Biol Philadelphia PA 19107 USA

There is growing awareness of the importance of noncoding (nc)rnas in the regulation of gene expression during pattern formation in development. Spatial regulation of Hox gene expression in development controls positional identity along the antero-posterior axis. In this review, we will focus on the role of short ncrnas that repress Hox genes in Drosophila and mammals by rna interference (rnai), on long ncrnas that may repress a Hox in cis in Drosophila by transcriptional interference, and on a novel long ncrna that functions in trans to regulate Hox genes mammals.

关键词： noncoding rna Hox mirna transcriptional interference epigenetic

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Roles of noncoding rnas in Ciliate Genome Architecture

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JOUrnaL OF MOLECULAR BIOLOGY 2020年第15期432卷 4186-4198页

作者： Allen, Sarah E. Nowacki, Mariusz Univ Bern Inst Cell Biol Bern Switzerland

Ciliates are an interesting model system for investigating diverse functions of noncoding rnas, especially in genome defence pathways. During sexual development, the ciliate somatic genome undergoes massive rearrangement and reduction through removal of transposable elements and other repetitive DNA. This is guided by a multitude of noncoding rnas of different sizes and functions, the extent of which is only recently becoming clear. The genome rearrangement pathways evolved as a defence against parasitic DNA, but interestingly also use the transposable elements and transposases to execute their own removal. Thus, ciliates are also a good model for the coevolution of host and transposable element, and the mutual dependence between the two. In this review, we summarise the genome rearrangement pathways in three diverse species of ciliate, with focus on recent discoveries and the roles of noncoding rnas. (C) 2020 The Author(s). Published by Elsevier Ltd.

关键词： ciliates noncoding rna genome rearrangement transposon defence

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The emerging regulatory roles of noncoding rnas in immune function of fish: Micrornas versus long noncoding rnas

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MOLECULAR GENETICS AND GENOMICS 2021年第4期296卷 765-781页

作者： Abo-Al-Ela, Haitham G. Suez Univ Dept Aquaculture Fac Fish Resources Genet & Biotechnol Suez 43518 Egypt

The genome could be considered as raw data expressed in proteins and various types of noncoding rnas (ncrnas). However, a large portion of the genome is dedicated to ncrnas, which in turn represent a considerable amount of the transcriptome. ncrnas are modulated on levels of type and amount whenever any physiological process occurs or as a response to external modulators. ncrnas, typically forming complexes with other partners, are key molecules that influence diverse cellular processes. Based on the knowledge of mammalian biology, ncrnas are known to regulate and control diverse trafficking pathways and cellular activities. Long noncoding rnas (lncrnas) notably have diverse and more regulatory roles than micrornas. Expanding these studies on fish has derived the same conclusion with relevance to other species, including invertebrates, explored the potentials to harness such types of rna to further understand the biology of such organisms, and opened gates for applying recent technologies, such as rna interference and delivering micromolecules as micrornas to living cells and possibly to target organs. These technologies should improve aquaculture productivity and fish health, as well as help understand fish biology.

关键词： Fish biology Gene regulation Long noncoding rnas Micrornas noncoding rna Transcriptome

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Potential Use of Antiapoptotic Proteins and noncoding rnas for Efficient In Vitro Follicular Maturation and Ovarian Bioengineering

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TISSUE ENGINEERING PART B-REVIEWS 2017年第2期23卷 142-158页

作者： Kim, Yoon Young Tamadon, Amin Ku, Seung-Yup Seoul Natl Univ Hosp Dept Obstet & Gynecol 28 Yonkeun Dong Seoul 110744 South Korea

In vitro culture of ovarian follicles is a promising bioengineering technique for preserving fecundity in reproductive-aged female by providing fertilizable oocytes. Successful clinical application should be preceded by developing the protocols that can efficiently overcome follicular cell apoptosis since the apoptosis is a critical phenomenon in in vivo folliculogenesis and in in vitro follicular maturation. Numerous prosurvival and antiapoptotic molecules, including follicular developmental regulators, have been reported to be involved in the intraovarian apoptosis. The authors searched literature and analyzed the current knowledge of these proteins and noncoding rnas, and their antiapoptotic roles in the dynamics of follicular development in vivo and in vitro. Two-dimensional (2D) culture method has widely been used, however, with recent emergence of various biomaterials, three-dimensional (3D) culture is also considered a proper environment for maintenance of solid structure of ovarian follicles. The identification of candidate paracrine and endocrine intracellular effectors that are responsible for the coordination occurring between oocyte, granulosa, and theca cells during follicular development was explored in this review, to assess the possibility of their use as antiapoptotic factors in establishing more efficacious 2D or 3D in vitro follicular microenvironment. The retrieved information will provide an inventory and the insight for defining more sophisticated culture conditions that are essential for functional artificial ovarian bioengineering.

关键词： antiapoptotic factor noncoding rna follicle ovary bioengineering

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Role of noncoding rnas in pancreatic ductal adenocarcinoma associated cachexia

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AMERICAN JOUrnaL OF PHYSIOLOGY-CELL PHYSIOLOGY 2022年第6期323卷 C1624-C1632页

作者： Uddin, Md. Hafiz Mohammad, Ramzi M. Philip, Philip A. Azmi, Asfar S. Muqbil, Irfana Wayne State Univ Karmanos Canc Inst Sch Med Dept Oncol Detroit MI USA Henry Ford Hlth Syst Detroit MI USA Lawrence Tech Univ Dept Nat Sci Southfield MI USA

Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, the majority of patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) cancer undergo cachexia. Pancreatic cancer causes deaths of similar to 50,000 Americans and about 400,000 people worldwide every year. The high mortality rates in metastatic PDAC are due to systemic pathologies and cachexia, which quickens death in these patients. About 90% of all patients with PDAC undergo wasting of muscle causing mobility loss and leading to a number of additional pathological conditions. PDAC-associated cancer cachexia emanates from complex signaling cues involving both mechanical and biological signals. Tumor invasion is associated with the loss of pancreatic function-induced digestive disorders and malabsorption, which causes subsequent weight loss and eventually promotes cachexia. Besides, systemic inflammation of patients with PDAC could release chemical cues (e.g., cytokine-mediated Atrogin-1/MAFbx expression) that participate in muscle wasting. Our understanding of genes, proteins, and cytokines involved in promoting cancer cachexia has evolved considerably. However, the role of epigenetic factors, particularly the role of noncoding rnas (ncrnas) in regulating PDAC-associated cachexia is less studied. In this review article, the most updated knowledge on the various ncrnas including micrornas (miRs), long noncoding rna (lncrnas), piwi interacting rnas (Piwirnas), small nucleolar rna (snornas), and circular rnas (circrna) and their roles in cancer cachexia are described.

关键词： cachexia muscle wasting noncoding rna pancreatic cancer tissue biopsy

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An Evaluation of Function of Multicopy noncoding rnas in Mammals Using ENCODE/FANTOM Data and Comparative Genomics

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MOLECULAR BIOLOGY AND EVOLUTION 2018年第6期35卷 1451-1462页

作者： Hoeppner, Marc P. Denisenko, Elena Gardner, Paul P. Schmeier, Sebastian Poole, Anthony M. Christian Albrechts Univ Kiel Inst Clin Mol Biol Kiel Germany Massey Univ Inst Nat & Math Sci Auckland New Zealand Univ Canterbury Sch Biol Sci Biomol Interact Ctr Christchurch New Zealand Univ Auckland Bioinformat Inst Sch Biol Sci Auckland New Zealand

Mammalian diversification has coincided with a rapid proliferation of various types of noncoding rnas, including members of both snrnas and snornas. The significance of this expansion however remains obscure. While some ncrna copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perhaps as a result of random retrotransposition. Hindering progress in our understanding of such observations is the difficulty in establishing function for the diverse features that have been identified in our own genome. Projects such as ENCODE and FANTOM have revealed a hidden world of genomic expression patterns, as well as a host of other potential indicators of biological function. However, such projects have been criticized, particularly from practitioners in the field of molecular evolution, where many suspect these data provide limited insight into biological function. The molecular evolution community has largely taken a skeptical view, thus it is important to establish tests of function. We use a range of data, including data drawn from ENCODE and FANTOM, to examine the case for function for the recent copy number expansion inmammals of six evolutionarily ancient rna families involved in splicing and rrna maturation. We use several criteria to assess evidence for function: conservation of sequence and structure, genomic synteny, evidence for transposition, and evidence for species-specific expression. Applying these criteria, we find that only aminority of loci show strong evidence for function and that, for the majority, we cannot reject the null hypothesis of no function.

关键词： evolution noncoding rna bioinformatics

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