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Post-transcriptional control of bacterial nitrogen metabolism by regulatory noncoding rnas

WORLD JOUrnaL OF MICROBIOLOGY & BIOTECHNOLOGY 2022年第7期38卷 126-126页

作者： Han, Yueyue Li, Chao Yan, Yongliang Lin, Min Ke, Xiubin Zhang, Yunhua Zhan, Yuhua Chinese Acad Agr Sci Biotechnol Res Inst Beijing Peoples R China Anhui Agr Univ Sch Resources & Environm Hefei Peoples R China

Nitrogen metabolism is the most basic process of material and energy metabolism in living organisms, and processes involving the uptake and use of different nitrogen sources are usually tightly regulated at the transcriptional and post-transcriptional levels. Bacterial regulatory noncoding rnas are novel post-transcriptional regulators that repress or activate the expression of target genes through complementarily pairing with target mrnas;therefore, these noncoding rnas play an important regulatory role in many physiological processes, such as bacterial substance metabolism and stress response. In recent years, a study found that noncoding rnas play a vital role in the post-transcriptional regulation of nitrogen metabolism, which is currently a hot topic in the study of bacterial nitrogen metabolism regulation. In this review, we present an overview of recent advances that increase our understanding on the regulatory roles of bacterial noncoding rnas and describe in detail how noncoding rnas regulate biological nitrogen fixation and nitrogen metabolic engineering. Furthermore, our goal is to lay a theoretical foundation for better understanding the molecular mechanisms in bacteria that are involved in environmental adaptations and metabolically-engineered genetic modifications.

关键词： Nitrogen metabolism Nitrogen fixation noncoding rna Post-transcriptional regulation

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N6-methyladenosine (m6A) modification in osteosarcoma: expression, function and interaction with noncoding rnas - an updated review

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EPIGENETICS 2023年第1期18卷 2260213页

作者： Zhang, Yuanzhuang Xu, Yeqiu Bao, Yuxin Luo, Yinzhou Qiu, Guanzhen He, Ming Lu, Jie Xu, Jian Chen, Bin Wang, Yong Shenyang Med Coll Cent Hosp Dept Orthoped Surg 4 5 South Seven West Rd Shenyang 110024 Liaoning Peoples R China Zhejiang Univ Affiliated Hosp 1 Coll Med Dept Orthoped Surg 58 Chengzhan Rd Hangzhou 310003 Zhejiang Peoples R China China Med Univ Shengjing Hosp Dept Orthoped Shenyang Liaoning Peoples R China China Med Univ Shenyang Peoples Hosp 4 Dept Cardiol Shenyang Liaoning Peoples R China

Osteosarcoma, originating from primitive bone-forming mesenchymal cells, is the most common malignant bone tumour among children and adolescents. N6-methyladenosine (m6A), the most ubiquitous type of posttranscriptional modification, is a methylation that occurs in the N6-position of adenosine. m6A dramatically affects the splicing, export, translation, and stability of various rnas, including mrna and noncoding rnas (ncrnas). Increasing evidence suggests that ncrnas, especially micrornas (mirna), long noncoding rnas (lncrna), and circular rnas (circrnas), regulate the m6A modification process by affecting the expression of m6A-associated enzymes. m6A modification interactions with ncrnas provide new perspectives for exploring the underlying mechanisms of tumorigenesis and progression. In the current review, we summarized the expression and biological functions of m6A regulators in osteosarcoma. At the same time, the present review systematically elucidated the functional and mechanical interactions between m6A modification and ncrnas in osteosarcoma. In addition, we discussed the effect of m6A and ncrnas in the tumour microenvironment and potential clinical applications of osteosarcoma.

关键词： Osteosarcoma N6-methyladenosine noncoding rna epigenetic regulation molecular mechanisms

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Identifying and annotating human bifunctional rnas reveals their versatile functions

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Science China(Life Sciences) 2016年第10期59卷 981-992页

作者： Geng Chen Juan Yang Jiwei Chen Yunjie Song Ruifang Cao Tieliu Shi Leming Shi Center for Pharmacogenomics School of Pharmacy and School of Life SciencesFudan UniversityShanghai 201203China The Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 201203China Fudan-Zhangjiang Center for Clinical Genomics Shanghai 201203China Zhanjiang Center for Translational Medicine Shanghai 201203China

Bifunctional rnas that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional rnas by integrating tandem mass spectrometry and rna-seq data. We first constructed a pipeline to identify and annotate bifunctional rnas,leading to the characterization of 132 high-confidence bifunctional rnas. Our analyses indicate that bifunctional rnas may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional rnas could interact with multiple mirnas and rna-binding proteins to exert their corresponding roles. Bifunctional rnas may also function as competing endogenous rnas to regulate the expression of many genes by competing for common targeting mirnas. Finally,somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional rnas. Collectively,our study not only provides the pipeline for identifying and annotating bifunctional rnas but also reveals their important gene-regulatory functions.

关键词： bifunctional rna noncoding rna rna-seq tandem mass spectrometry

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Regulation of poly(a)-specific ribonuclease activity by reversible lysine acetylation

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2020年第30期295卷 10255-10270页

作者： Dejene, Eden A. Li, Yixuan Showkatian, Zahra Ling, Hongbo Seto, Edward George Washington Univ Sch Med & Hlth Sci Dept Biochem & Mol Med Washington DC 20052 USA George Washington Univ Canc Ctr Washington DC 20052 USA

Poly(A)-specific ribonuclease (PARN) is a 3?-exoribonuclease that plays an important role in regulating the stability and maturation of rnas. Recently, PARN has been found to regulate the maturation of the human telomerase rna component (hTR), a noncoding rna required for telomere elongation. Specifically, PARN cleaves the 3?-end of immature, polyadenylated hTR to form the mature, nonpolyadenylated template. Despite PARN's critical role in mediating telomere maintenance, little is known about how PARN's function is regulated by post-translational modifications. In this study, using shrna- and CRISPR/Cas9-mediated gene silencing and knockout approaches, along with 3?-exoribonuclease activity assays and additional biochemical methods, we examined whether PARN is post-translationally modified by acetylation and what effect acetylation has on PARN's activity. We found PARN is primarily acetylated by the acetyltransferase p300 at Lys-566 and deacetylated by sirtuin1 (SIRT1). We also revealed how acetylation of PARN can decrease its enzymatic activity bothin vitro,using a synthetic rna probe, andin vivo,by quantifying endogenous levels of adenylated hTR. Furthermore, we also found that SIRT1 can regulate levels of adenylated hTR through PARN. The findings of our study uncover a mechanism by which PARN acetylation and deacetylation regulate its enzymatic activity as well as levels of mature hTR. Thus, PARN's acetylation status may play a role in regulating telomere length.

关键词： post-translational modification (PTM) protein acetylation p300 sirtuin1 (SIRT1) polyadenylation rna processing human telomerase rna component (hTR) poly(A)-specific ribonuclease (PARN) genome maintenance noncoding rna acetylation sirtuin 1 (SIRT1)

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Conditional Hfq Association with Small noncoding rnas in Pseudomonas aeruginosa Revealed through Comparative UV Cross-Linking Immunoprecipitation Followed by High-Throughput Sequencing

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MSYSTEMS 2019年第6期4卷 e00590-19页

作者： Chihara, Kotaro Bischler, Thorsten Barquist, Lars Monzon, Vivian A. Noda, Naohiro Vogel, Jorg Tsuneda, Satoshi Waseda Univ Dept Life Sci & Med Biosci Tokyo Japan Natl Inst Adv Ind Sci & Technol Biomed Res Inst Tsukuba Japan Univ Hosp Wurzburg Core Unit Syst Med Wurzburg Germany Helmholtz Ctr Infect Res Helmholtz Inst RNA Based Infect Res Wurzburg Germany Univ Wurzburg Fac Med Wurzburg Germany European Bioinformat Inst European Mol Biol Lab Hinxton England Univ Wurzburg Inst Mol Infect Biol Wurzburg Germany

Bacterial small noncoding rnas (srnas) play posttranscriptional regulatory roles in cellular responses to changing environmental cues and in adaptation to harsh conditions. Generally, the rna-binding protein Hfq helps srnas associate with target mrnas to modulate their translation and to modify global rna pools depending on physiological state. Here, a combination of in vivo UV cross-linking immunoprecipitation followed by high-throughput sequencing (CLIP-seq) and total rna-seq showed that Hfq interacts with different regions of the Pseudomonas aeruginosa transcriptome under planktonic versus biofilm conditions. In the present approach, P. aeruginosa Hfq preferentially interacted with repeats of the AAN triplet motif at mrna 5' untranslated regions (UTRs) and srnas and U-rich sequences at rho-independent terminators. Further transcriptome analysis suggested that the association of srnas with Hfq is primarily a function of their expression levels, strongly supporting the notion that the pool of Hfq-associated rnas is equilibrated by rna concentration-driven cycling on and off Hfq. Overall, our combinatorial CLIP-seq and total rna-seq approach highlights conditional srna associations with Hfq as a novel aspect of posttranscriptional regulation in P. aeruginosa. IMPORTANCE The Gram-negative bacterium P. aeruginosa is ubiquitously distributed in diverse environments and can cause severe biofilm-related infections in at-risk individuals. Although the presence of a large number of putative srnas and widely conserved rna chaperones in this bacterium implies the importance of posttranscriptional regulatory networks for environmental fluctuations, limited information is available regarding the global role of rna chaperones such as Hfq in the P. aeruginosa transcriptome, especially under different environmental conditions. Here, we characterize Hfq-dependent differences in gene expression and biological processes in two physiological states: the planktonic and biofilm forms.

关键词： CLIP-seq Hfq Pseudomonas aeruginosa biofilms noncoding rna

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RedChIP identifies noncoding rnas associated with genomic sites occupied by Polycomb and CTCF proteins

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2022年第1期119卷 e2116222119-e2116222119页

作者： Gavrilov, Alexey A. Sultanov, Rinat, I Magnitov, Mikhail D. Galitsyna, Aleksandra A. Dashinimaev, Erdem B. Aiden, Erez Lieberman Razin, Sergey, V Russian Acad Sci Inst Gene Biol Moscow 119334 Russia Fed Med Biol Agcy Fed Res & Clin Ctr Phys Chem Med Moscow 119435 Russia Pirogov Russian Natl Res Med Univ Ctr Precis Genome Editing & Genet Technol Biomed Moscow 117997 Russia Baylor Coll Med Ctr Genome Architecture Dept Mol & Human Genet Houston TX 77030 USA Rice Univ Ctr Theoret Biol Phys Dept Comp Sci Houston TX 77030 USA Lomonosov Moscow State Univ Fac Biol Moscow 119991 Russia

Nuclear noncoding rnas (ncrnas) are key regulators of gene expression and chromatin organization. The progress in studying nuclear ncrnas depends on the ability to identify the genome-wide spectrum of contacts of ncrnas with chromatin. To address this question, a panel of rna-DNA proximity ligation techniques has been developed. However, neither of these techniques examines proteins involved in rna-chromatin interactions. Here, we introduce RedChIP, a technique combining rna-DNA proximity ligation and chromatin immunoprecipitation for identifying rna-chromatin interactions mediated by a particular protein. Using antibodies against architectural protein CTCF and the EZH2 subunit of the Polycomb repressive complex 2, we identify a spectrum of cis- and trans-acting ncrnas enriched at Polycomb- and CTCF-binding sites in human cells, which may be involved in Polycomb-mediated gene repression and CTCF-dependent chromatin looping. By providing a protein-centric view of rna-DNA interactions, RedChIP represents an important tool for studies of nuclear ncrnas.

关键词： noncoding rna cell nucleus rna-DNA interactome CTCF Polycomb

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Emerging noncoding rnas contained in extracellular vesicles: rising stars as biomarkers in lung cancer liquid biopsy

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THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY 2022年 14卷 17588359221131229页

作者： Cammarata, Giuseppe De Miguel-Perez, Diego Russo, Alessandro Peleg, Ariel Dolo, Vincenza Rolfo, Christian Taverna, Simona Natl Res Council CNR Italy Inst Translat Pharmacol IFT Via Ugo La Malta 153 I-90146 Palermo Italy Icahn Sch Med Mt Sinai Ctr Thorac Oncol Tisch Canc Inst One Gustave Levy PlBox 1079 New York NY 10029 USA Univ Messina AO Papardo & Dept Human Pathol Med Oncol Unit Messina Italy Univ Aquila Dept Life Hlth & Environm Sci Laquila Italy

Lung cancer has a high morbidity and mortality rate, and affected patients have a poor prognosis and low survival. The therapeutic approaches for lung cancer treatment, including surgery, radiotherapy, and chemotherapy, are not completely effective, due to late diagnosis. Although the identification of genetic drivers has contributed to the improvement of lung cancer clinical management, the discovery of new diagnostic and prognostic tools remains a critical issue. Liquid biopsy (LB) represents a minimally invasive approach and practical alternative source to investigate tumor-derived alterations and to facilitate the selection of targeted therapies. LB allows for the testing of different analytes such as circulating tumor cells, extracellular vesicles (EVs), tumor-educated platelets, and cell-free nucleic acids including DNAs, rnas, and noncoding rnas (ncrnas). Several regulatory factors control the key cellular oncogenic pathways involved in cancers. ncrnas have a wide range of regulatory effects in lung cancers. This review focuses on emerging regulatory ncrnas, freely circulating in body fluids or shuttled by EVs, such as circular-rnas, small nucleolar-rnas, small nuclear-rnas, and piwi-rnas, as new biomarkers for early detection, prognosis, and monitoring of therapeutic strategy of lung cancer treatment.

关键词： extracellular vesicles liquid biopsy lung cancer noncoding rna circular-rna piwi rna

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Unraveling diverse roles of noncoding rnas in various human papillomavirus negative cancers

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PHARMACOLOGY & THERAPEUTICS 2022年 238卷 108188页

作者： Chen, Xin Liu, Yi Liu, Hejing Wang, Zhi-wei Zhu, Xueqiong Wenzhou Med Univ Dept Obstet & Gynecol Affiliated Hosp 2 Wenzhou 325027 Peoples R China Beijing Zhongwei Res Ctr Biol & Translat Med Dept Res & Dev Beijing 100161 Peoples R China

Human papillomavirus (HPV)-negative tumors distinguish from cancers associated with HPV infection. Due to its high rate of lymph node metastasis and difficulty in inchoate discover and diagnosis, the treatment efficacy of HPV-negative cancers is unsatisfactory. Epidemiological evidence suggests that HPV-negative tumor patients have a poor prognosis, and the mortality is higher than that of cancer patients caused by HPV infection. Evidence has demonstrated that noncoding rnas (ncrnas) play a crucial role in regulation of physiological and developmental processes. Therefore, dysregulated ncrnas are involved in the occurrence of diversified diseases, including cancer. In cumulative studies, ncrnas are concerned with pathogenetic mechanisms of HPV-negative tumors via regulating gene expression and signal transduction. It is important to decipher the functions of ncrnas in HPV-negative cancers and identify the potential biomarkers, which will bring new treatment strategies for improving outcome of cancer therapy. In this review, we demonstrated the effects of ncrnas via regulating the development and progression of HPV- negative tumors by directly or indirectly acting on target molecules, which provide a basis for future tumor targeted therapy by targeting ncrnas for HPV-negative cancers. (c) 2022 Elsevier Inc. All rights reserved.

关键词： HPV-negative cancer Carcinogenesis noncoding rna Lncrnas mirnas

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Promoted Adipogenesis of Rat Mesenchymal Stem Cells by Transfection of Small Interfering rna Complexed with a Cationized Dextran

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TISSUE ENGINEERING PART A 2010年第1期16卷 21-31页

作者： Nagane, Kentaro Jo, Jun-ichiro Tabata, Yasuhiko Kyoto Univ Inst Frontier Med Sci Field Tissue Engn Dept BiomatSakyo Ku Kyoto 6068507 Japan

The objective of this study is to investigate the possibility of small interfering rna (sirna) complexed with a cationized dextran of nonviral carrier to biologically modify the adipogenesis extent of bone marrow-derived mesenchymal stem cells (MSC). Spermine was chemically introduced to the hydroxyl groups of dextran to prepare the cationized dextran (spermine-dextran). The spermine-dextran could form a complex with sirna, and the physicochemical properties were changed by the molecular weight of dextran, the molar percentage of spermine introduced to dextran, and the molar ratio of nitrogen molecule of spermine-dextran to the phosphorous ones of sirna (N/P ratio). The gene expression level of luciferase or green fluorescence protein was significantly suppressed by transfection with the complex of spermine-dextran and sirna. The gene expression level by the complex decreased with an increase in the extent of complex internalized. Biochemical experiments revealed that culture in an adipogenic differentiation medium allowed MSC to differentiate into adipogenic cells. However, upon culturing with sirna of anti-transcription coactivator containing PDZ-binding motif (TAZ) for osteogenic differentiation complexed with the spermine-dextran, the adipogenesis of MSC was further promoted. It is concluded that the spemine-dextran was a promising nonviral carrier to suppress the expression level of differentiation gene, resulting in the modification of cell differentiation direction.

关键词： Cellular phenomena Mesenchymal stem cell noncoding rna

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Genome-wide identification and functional prediction of circular rnas in response to heat stress in Chinese Holstein cows

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ANIMAL BIOTECHNOLOGY 2022年第6期33卷 1170-1180页

作者： Qi, Ying Zhang, Lin Guo, Yuemei Wang, Jing Chu, Mingxing Zhang, Yiming Guo, Junfei Li, Qiuling Langfang Normal Univ Coll Life Sci Hebei Key Lab Anim Divers Langfang Key Lab Cell Engn & Applicat Aiminxi Rd Langfang 065000 Peoples R China Chinese Acad Agr Sci Inst Anim Sci Key Lab Anim Poultry Genet Breeding & Reprod Minist Agr & Rural Affairs Beijing Peoples R China Guangdong Women & Children Hosp Clin Lab Dept 521 Xingnan Rd Guangzhou 510000 Peoples R China

Heat stress (HS) leads to substantial economic loss of dairy industry each year. The negative effect of HS in dairy cows is becoming one of the more urgent issue due to accelerating side-effects of global warming. Various genes are involved in HS response but the information about the role of noncoding rnas, especially circular rnas (circrnas) is largely unknown. In our study, we aimed to investigate the different expression profile of circrnas between HS and Non-heat-stressed condition (NC) of Chinese Holstein cow's mammary gland. Circrnas were identified using rna sequencing and bioinformatics analysis. In total, 37405 circrnas were detected and 95 were differentially expressed (DE), including 15 downregulated and 80 upregulated circrnas in HS group compared to NC. Eight circrnas were randomly selected to verify the rna sequencing result. Further, Sanger sequencing validated the backsplicing site of the eight circrnas. Moreover, results obtained from the Quantitative real time PCR (qRT-PCR) showed consistent expression trend with that of rna sequencing. GO annotation and KEGG analysis suggested that these DE circrnas probably involved in the energy metabolic regulation. Furthermore, we constructed cerna network and the result indicated that these DE circrnas could regulate lactation through IGF1 and PRL signaling pathway.

关键词： Heat stress circrnas mammary gland noncoding rna dairy cows

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