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cncRNAs: Bi-functional RNAs with protein coding and non-coding functions

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY 2015年 47-48卷 40-51页

作者： Kumari, Pooja Sampath, Karuna Univ Warwick Warwick Med Sch Div Biomed Cell Biol Coventry CV4 7AJ W Midlands England

For many decades, the major function of mRNA was thought to be to provide protein-coding information embedded in the genome. The advent of high-throughput sequencing has led to the discovery of pervasive transcription of eukaryotic genomes and opened the world of RNA-mediated gene regulation. Many regulatory RNAs have been found to be incapable of protein coding and are hence termed as non-coding RNAs (ncRNAs). However, studies in recent years have shown that several previously annotated noncoding RNAs have the potential to encode proteins, and conversely, some coding RNAs have regulatory functions independent of the protein they encode. Such bi-functional RNAs, with both protein coding and non-coding functions, which we term as 'cncRNAs', have emerged as new players in cellular systems. Here, we describe the functions of some cncRNAs identified from bacteria to humans. Because the functions of many RNAs across genomes remains unclear, we propose that RNAs be classified as coding, non-coding or both only after careful analysis of their functions. (C) 2015 The Authors. Published by Elsevier Ltd.

关键词： cncRNAs Bi-functional RNA Non coding RNA protein coding Regulatory RNA RNA structure RNA processing Dual function RNA

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Different roles of circular RNAs with protein coding potentials

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2018年第4期500卷 907-909页

作者： Bagchi, Angshuman Univ Kalyani Dept Biochem & Biophys Kalyani 741235 Nadia India

Circular RNAs are a class of recently identified long non-coding RNAs. Various experiments reveled that they are covalently closed molecules and are resistant to attack by exonucleases. These RNA molecules are linked to various diseases. Interestingly, though they belong to the class of non-coding RNAs, some of them are experimentally verified to code for protein products. Till date there are no reports regarding the structural aspects of the protein products from these circular RNA molecules. In this work, an attempt has been made to analyze the structural details of the proteins obtained from the circular RNA molecules. Only those circular RNAs were selected for which there was direct experimental evidences of generation of protein products. The work for the first time elucidates the molecular details of the protein products obtained from circular RNA molecules. (C) 2018 Elsevier Inc. All rights reserved.

关键词： Circular RNA Long non-coding RNA protein coding Structural details Molecular mechanism

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Evidence for two protein coding transcripts at the Igf2as locus

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GENE REPORTS 2016年 4卷 60-66页

作者： Carolina, Duart-Garcia Philippe, Plattet Remy, Bruggmann Cedric, Simillion A. M. V. Irene, Keller Goran, Andersson Martin, Braunschweig H. Univ Bern Vetsuisse Fac Inst Genet Bremgartenstr 109a CH-3001 Bern Switzerland Univ Bern Theodor Kocher Inst Grad Sch Cellular & Biomed Sci Freiestr 1 CH-3012 Bern Switzerland Univ Bern Vetsuisse Fac DCR VPH Div Neurol Sci Bremgartenstr 109a CH-3001 Bern Switzerland Univ Bern Dept Biol Baltzerstr 6 CH-3012 Bern Switzerland Univ Bern Dept Clin Res Murtenstr 35 CH-3010 Bern Switzerland Swedish Univ Agr Sci Dept Anim Breeding & Genet Ulls Vag 26 S-75007 Uppsala Sweden

The insulin-like growth factor 2 antisense (Igf2as) gene is part of the Ins-Igf2-H19 imprinted gene cluster. The function of the paternally expressed Igf2as is still elusive. In our previouswork, we showed that Igf2as transcripts were located in the cytoplasm of C2C12 mouse myoblast cells, associated with polysomes and polyadenylated suggesting that Igf2as is protein coding. In the presentwork, the protein coding capacity of Igf2aswas investigated. We demonstrate for the first time the existence of a polypeptide translated froman Igf2as construct. Furthermore, an RNA-Seq analysiswas performed using RNA prepared from skeletal muscles of newborn wild-type ***1-U2 mice to further elucidate the function of Igf2as transcripts. We found no evidence for a regulatory role of Igf2as in the imprinted gene cluster. Interestingly, the RNA-Seq analysis indicated that Igf2as plays a role in the energymetabolism, the cell cycle, histone acetylation and muscle contraction pathways. Our Igf2as investigations further elucidated that there are two distinct Igf2as transcripts corresponding to two putative ORFs. (C) 2016 Elsevier Inc. All rights reserved.

关键词： Igf2as protein coding Transcription RNA-Seq

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Utility of the nuclear protein-coding gene, elongation factor-1 gamma (EF-1γ), for spider systematics, emphasizing family level relationships of tarantulas and their kin (Araneae: Mygalomorphae)

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MOLECULAR PHYLOGENETICS AND EVOLUTION 2007年第2期42卷 394-409页

作者： Ayoub, Nadia A. Garb, Jessica E. Hedin, Marshal Hayashi, Cheryl Y. Univ Calif Riverside Dept Biol Riverside CA 92521 USA San Diego State Univ Dept Biol San Diego CA 92182 USA

Spider systematics has overwhelmingly relied on morphological characters to resolve higher-level phylogenetic questions. Molecular phylogenetic studies of spiders above the genus level have been rare, partly because of a paucity of characterized genes available for amplification and sequencing. Here we show the phylogenetic utility of a new molecular marker, elongation factor-1 gamma (EF-1 gamma) for discerning family level relationships in the spider infraorder, Mygalomorphae. We included genomic sequences from 26 mygalomorph genera in 14 families as well as cDNA sequences from 10 families in the infraorder Arancomorphae. We found strong support for the traditional split of mygalomorphs into atypoids (Antrodiaetidae, Atypidae, and Mecicobothriidae) and non-atypoids (all other families). Some families with multiple generic representatives were found to be polyphyletic or paraphyletic, such as the Nemesiidae, Ctenizidae, and Hexathelidae. A small portion of genomic EF-1 gamma that could be amplified from araneomorphs contained a short intron, suggesting that longer genomic sequences could not be amplified due to the presence of introns. This intron may be useful for intra-familial araneomorph relationships. A tentative timeline for spider evolution is proposed using the evolutionary rate of EF-1 gamma, estimated to be approximately 0.22% pairwise divergence per million years based on a non-parametric smoothing method (NPRS) and fossil constraints. (c) 2006 Elsevier Inc. All rights reserved.

关键词： EST molecular clock nuclear gene Opisthothelae protein coding substitution rate arthropod

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Identification of the protein coding capability of coronavirus defective viral genomes by mass spectrometry

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Virology journal 2023年第1期20卷 290页

作者： Ching-Hung Lin Feng-Cheng Hsieh Chien-Chen Lai Wei-Chen Wang Cheng-Yu Kuo Chun-Chun Yang Hsuan-Wei Hsu Hon-Man-Herman Tam Cheng-Yao Yang Hung-Yi Wu Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University Taichung 40227 Taiwan. Institute of Molecular Biology College of Life Sciences National Chung Hsing University Taichung 40227 Taiwan. Department of Veterinary Medicine College of Veterinary Medicine National Chung Hsing University Taichung 40227 Taiwan. Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University Taichung 40227 Taiwan. yangchengyao@dragon.nchu.edu.tw. Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University Taichung 40227 Taiwan. hwu2@dragon.nchu.edu.tw.

During coronavirus infection, in addition to the well-known coronavirus genomes and subgenomic mRNAs, an abundance of defective viral genomes (DVGs) can also be synthesized. In this study, we aimed to examine whether DVGs can encode proteins in infected cells. Nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were employed. With the protein databases generated by nanopore direct RNA sequencing and the cell lysates derived from the RNA-protein pull-down assay, six DVG-encoded proteins were identified by LC-MS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The results suggest that the coronavirus DVGs have the capability to encode proteins. Consequently, future studies determining the biological function of DVG-encoded proteins may contribute to the understanding of their roles in coronavirus pathogenesis and the development of antiviral strategies.

关键词： Coronavirus Defective viral genome Gene expression Pathogenesis protein coding

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protein Classification with Extended-Sequence coding by Sliding Window

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IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2011年第6期8卷 1721-1726页

作者： Rodrigues, Thiago de Souza Cardoso, Fernanda Caldas Ribeiro Teixeira, Santuza Maria Oliveira, Sergio Costa Braga, Antonio Padua Fed Ctr Technol Educ Minas Gerais Dept Comp BR-30421169 Belo Horizonte MG Brazil Univ Fed Minas Gerais Biochem & Immunol Dept BR-31270901 Belo Horizonte MG Brazil Univ Fed Minas Gerais Dept Elect Engn BR-31270901 Belo Horizonte MG Brazil

A large number of unclassified sequences is still found in public databases, which suggests that there is still need for new investigations in the area. In this contribution, we present a methodology based on Artificial Neural Networks for protein functional classification. A new protein coding scheme, called here Extended-Sequence coding by Sliding Windows, is presented with the goal of overcoming some of the difficulties of the well method Sequence coding by Sliding Window. The new protein coding scheme uses more than one sliding window length with a weight factor that is proportional to the window length, avoiding the ambiguity problem without ignoring the identity of small subsequences Accuracy for Sequence coding by Sliding Windows ranged from 60.1 to 77.7 percent for the first bacterium protein set and from 61.9 to 76.7 percent for the second one, whereas the accuracy for the proposed Extended-Sequence coding by Sliding Windows scheme ranged from 70.7 to 97.1 percent for the first bacterium protein set and from 61.1 to 93.3 percent for the second one. Additionally, protein sequences classified inconsistently by the Artificial Neural Networks were analyzed by CD-Search revealing that there are some disagreement in public repositories, calling the attention for the relevant issue of error propagation in annotated databases due the incorrect transferred annotations.

关键词： Artificial neural network protein functional classification protein coding protein functional classification error

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A novel protein encoded by circARHGAP12 attenuates DNA damage and apoptosis by regulating MDC1 in intestinal ischemia/reperfusion injury

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 2025年 286卷 138374页

作者： Liu, Deshun Zhao, Xuzi Wang, Zhecheng Wang, Guangzhi Chen, Zhao Ning, Shili Feng, Dongcheng Sun, Xin Sun, Ruimin Yao, Jihong Tian, Xiaofeng Dalian Med Univ Dept Gen Surg Affiliated Hosp 2 Dalian 116023 Peoples R China Dalian Med Univ Dept Pharmacol Dalian 116044 Peoples R China Dalian Med Univ Dept Gen Surg Affiliated Hosp 1 Dalian 116600 Peoples R China

Excessive intestinal ischemia/reperfusion (I/R)-induced epithelial cell apoptosis results in damage to the intestinal defense barrier. Circular RNAs (circRNAs) are functional RNA transcripts, and their functions as microRNA (miRNA) sponges and binding proteins have been well characterized. Recent evidence has indicated that some circRNAs encode functional proteins. However, whether protein-encoding circRNAs contribute to intestinal I/R remains undiscovered. Here, we identified a protein-encoding circRNA, circARHGAP12, that can significantly attenuate intestinal I/R-induced cell apoptosis. Moreover, circARHGAP12 can encode a 229-amino-acid (aa) protein, ARHGAP12-229aa. The expression of both circARHGAP12 and ARHGAP12-229aa was downregulated in intestinal I/R injury. Additionally, circARHGAP12 protected against intestinal I/R injury mainly by encoding ARHGAP12-229aa. We performed RNA sequencing (RNA-seq) analyses to identify downstream targets of ARHGAP12-229aa. The results revealed that overexpression of ARHGAP12-229aa led to increased expression of MDC1, a DNA damage-related protein, and that this increase was accompanied by a decrease in intestinal epithelial cell DNA damage and apoptosis. Furthermore, MDC1 silencing weakened the protective effect of ARHGAP12-229aa against intestinal I/R injury. Our findings suggest a novel perspective on circRNA function, providing an innovative therapeutic strategy for intestinal I/R.

关键词： Intestinal ischemia/reperfusion (I/R) Circular RNA (circRNA) protein coding Apoptosis DNA damage

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Combining independent de novo assemblies optimizes the coding transcriptome for nonconventional model eukaryotic organisms

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BMC BIOINFORMATICS 2016年第1期17卷 1-13页

作者： Cerveau, Nicolas Jackson, Daniel J. Georg August Univ Gottingen Dept Geobiol Goldschmidtstr 3 D-37077 Gottingen Germany

Background: Next-generation sequencing (NGS) technologies are arguably the most revolutionary technical development to join the list of tools available to molecular biologists since PCR. For researchers working with nonconventional model organisms one major problem with the currently dominant NGS platform (Illumina) stems from the obligatory fragmentation of nucleic acid material that occurs prior to sequencing during library preparation. This step creates a significant bioinformatic challenge for accurate de novo assembly of novel transcriptome data. This challenge becomes apparent when a variety of modern assembly tools (of which there is no shortage) are applied to the same raw NGS dataset. With the same assembly parameters these tools can generate markedly different assembly outputs. Results: In this study we present an approach that generates an optimized consensus de novo assembly of eukaryotic coding transcriptomes. This approach does not represent a new assembler, rather it combines the outputs of a variety of established assembly packages, and removes redundancy via a series of clustering steps. We test and validate our approach using Illumina datasets from six phylogenetically diverse eukaryotes (three metazoans, two plants and a yeast) and two simulated datasets derived from metazoan reference genome annotations. All of these datasets were assembled using three currently popular assembly packages (CLC, Trinity and IDBA-tran). In addition, we experimentally demonstrate that transcripts unique to one particular assembly package are likely to be bioinformatic artefacts. For all eight datasets our pipeline generates more concise transcriptomes that in fact possess more unique annotatable protein domains than any of the three individual assemblers we employed. Another measure of assembly completeness (using the purpose built BUSCO databases) also confirmed that our approach yields more information. Conclusions: Our approach yields coding transcriptome assembli

关键词： Transcriptome De novo assembly Eukaryote protein coding Merge Redundant

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Exploration for Functional Nucleotide Sequence Candidates within coding Regions of Mammalian Genes

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DNA RESEARCH 2011年第3期18卷 177-187页

作者： Suzuki, Rumiko Saitou, Naruya Grad Univ Adv Studies Dept Genet Sch Life Sci Mishima Shizuoka 4118540 Japan Natl Inst Genet Div Populat Genet Mishima Shizuoka 4118540 Japan

The primary role of a protein coding gene is to encode amino acids. Therefore, synonymous sites of codons, which do not change the encoded amino acid, are regarded as evolving neutrally. However, if a certain region of a protein coding gene contains a functional nucleotide element (e.g. splicing signals), synonymous sites in the region may have selective pressure. The existence of such elements would be detected by searching regions of low nucleotide substitution. We explored invariant nucleotide sequences in 10 790 orthologous genes of six mammalian species (Homo sapiens, Macaca mulatta, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris), and extracted 4150 sequences whose conservation is significantly stronger than other regions of the gene and named them significantly conserved coding sequences (SCCSs). SCCSs are observed in 2273 genes. The genes are mainly involved with development, transcriptional regulation, and the neurons, and are expressed in the nervous system and the head and neck organs. No strong influence of conventional factors that affect synonymous substitution was observed in SCCSs. These results imply that SCCSs may have double function as nucleotide element and protein coding sequence and retained in the course of mammalian evolution.

关键词： mammal protein coding nucleotide conservation

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A protein encoded by circular ZNF609 RNA induces acute kidney injury by activating the AKT/mTOR-autophagy pathway

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MOLECULAR THERAPY 2023年第6期31卷 1722-1738页

作者： Ouyang, Xin He, Zhimei Fang, Heng Zhang, Huidan Yin, Qi Hu, Linhui Gao, Fei Yin, Hao Hao, Taofang Hou, Yating Wu, Qingrui Deng, Jia Xu, Jing Wang, Yirong Chen, Chunbo Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Guangdong Cardiovasc Inst Dept Intens Care Unit Cardiac Surg 96 Dongchuan Rd Guangzhou 510080 Guangdong Peoples R China Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Dept Crit Care Med 106 Zhongshan Er Rd Guangzhou 510080 Guangdong Peoples R China Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Res Ctr Med Sci 106 Zhongshan Er Rd Guangzhou 510080 Guangdong Peoples R China CookGene Biosci Ctr Guangzhou 510320 Guangdong Peoples R China Forevergen Biosci Ctr Guangzhou 510320 Guangdong Peoples R China Maoming Peoples Hosp Dept Crit Care Med Maoming 525000 Guangdong Peoples R China Maoming Peoples Hosp Dept Sci Res Ctr Maoming 525000 Guangdong Peoples R China Southern Med Univ Sch Clin Med 2 Guangzhou 510515 Guangdong Peoples R China

Autophagy plays a crucial role in the development and progres-sion of ischemic acute kidney injury (AKI). However, the func-tion and mechanism of circular RNAs (circRNAs) in the regu-lation of autophagy in ischemic AKI remain unexplored. Herein, we find that circ-ZNF609, originating from the ZNF609 locus, is highly expressed in the kidney after ischemia/reperfusion injury, and urinary circ-ZNF609 is a moderate predictor for AKI in heart disease patients. Overex-pression of circ-ZNF609 can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis while inhibiting proliferation in HK-2 cells, which is blocked by silencing circ-ZNF609. Mechanistically, circ-ZNF609 encodes a functional protein consisting of 250 amino acids (aa), termed ZNF609-250aa, the overexpression of which can activate AKT3/mTOR signaling and induce autophagy flux impairment and cell apoptosis in HK-2 cells in vitro and in AKI kidneys in vivo. The blockade of AKT and mTOR signaling with phar-macological inhibitors is capable of reversing ZNF609-250aa-induced autophagy flux impairment and cell apoptosis in HK-2 cells. The present study demonstrates that highly ex-pressed circ-ZNF609-encoded ZNF609-250aa induces cell apoptosis and AKI by impairing the autophagy flux via an AKT/mTOR-dependent mechanism. These findings imply that targeting circ-ZNF609 may be a novel therapy for ischemic AKI.

关键词： acute kidney injury renal ischemia/reperfusion circRNA protein coding autophagy

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