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The distinct transcriptomes of slow and fast adult muscles are delineated by noncoding rnas

FASEB JOUrnaL 2018年第3期32卷 1579-1590页

作者： Raz, Vered Riaz, Muhammad Tatum, Zuotian Kielbasa, Szymon M. 't Hoen, Peter A. C. Leiden Univ Med Ctr Dept Human Genet Einthovenweg 20 NL-2333 ZC Leiden Netherlands Leiden Univ Med Ctr Dept Med Stat & Bioinformat Bioinformat Ctr Expertise Leiden Netherlands

Adult muscles have a vast adaptation capacity, enabling function switches in response to altered conditions. During intensive physical activity, disease, or aging, adult skeletal muscles change and adjust their functions. The competence to adjust varies among muscles. Muscle-specific molecular mechanisms in healthy and normal conditions could designate changes in physiologic and pathologic conditions. We generated deep mrna-sequencing data in adult fast and slow mouse muscles, and applying paired analysis, we identified that the muscle specific signatures are composed of half of the muscle transcriptome. The fast muscles showed a more compact gene network that is concordant with homogenous myofiber typing, compared with the pattern in the slow muscle. The muscle-specific mrna landscape did not correlate with alternative spicing, alternative polyadenylation, or the expression of muscle transcription factor gene networks. However, we found significant correlation between the differentially expressed noncoding rnas, micrornas (mirnas) and long noncoding rnas (lncrnas) and their target genes. More than 25% of the genes expressed in amuscle-specific fashion were found to be targets of muscle specific mirnas and lncrnas. We suggest that muscle-specific mirnas and lncrnas contribute to the establishment of muscle-specific transcriptomes in adult muscles.

关键词： skeletal muscles fiber type mrna processing rnaseq noncoding rna

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Prognostic value and immune infiltration of novel signatures in colon cancer microenvironment

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CANCER CELL INTErnaTIONAL 2021年第1期21卷 679-679页

作者： Lin, Yilin Pan, Xiaoxian Chen, Zhihua Lin, Suyong Shen, Zhanlong Chen, Shaoqin Fujian Med Univ Dept Surg Gastroenterol Affiliated Hosp 1 20 Chazhong Rd Fuzhou Fujian Peoples R China Peking Univ Peoples Hosp Dept Surg Gastroenterol 11 Xizhimen South St Beijing Peoples R China Fujian Med Univ Dept Radiotherapy Affiliated Hosp 1 Fuzhou Fujian Peoples R China

Background Growing evidence has shown that the prognosis for colon cancer depends on changes in microenvironment. The purpose of this study was to elucidate the prognostic value of long noncoding rnas (lncrnas) related to immune microenvironment (IM) in colon cancer. Methods Single sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of colon cancer based on the immune genomes of 29 immune signatures. Cox regression analysis identified a lncrna signatures associated with immune infiltration. The Tumor Immune Estimation Resource database was used to analyze immune cell content. Results Colon cancer samples were divided into three subtypes by unsupervised cluster analysis. Cox regression analysis identified an immune infiltration-related 5-lncrna signature. This signature combined with clinical factors can effectively improve the predictive ability for the overall survival (OS) of colon cancer. At the same time, we found that the expression of H19 affects the content of B cells and macrophages in the microenvironment of colon cancer and affects the prognosis of colon cancer. Finally, we constructed the H19 regulatory network and further analyzed the possible mechanisms. We found that knocking down the expression of H19 can significantly inhibit the expression of CCND1 and VEGFA. At the same time, the immunohistochemical assay found that the expression of CCND1 and VEGFA protein was significantly positively correlated with the infiltration of M2 type macrophages. Conclusion The findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer.

关键词： Colon cancer Tumor microenvironment noncoding rna H19 Immune infiltration Survival

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Diagnostic and prognostic blood biomarkers in vascular dementia: From the viewpoint of ischemic stroke

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NEUROCHEMISTRY INTErnaTIONAL 2021年 146卷 105015-105015页

作者： Hosoki, Satoshi Tanaka, Tomotaka Ihara, Masafumi Natl Cerebral & Cardiovasc Ctr Dept Neurol 6-1 Kishibe Shimmachi Suita Osaka 5648565 Japan

Reliable quantitative blood biomarkers are important in vascular dementia (VaD) because early diagnosis and therapeutic intervention are effective in preventing progression of dementia. Although many blood biomarkers for acute ischemic stroke (AIS) or VaD have been reported, there are few reliable blood biomarkers. VaD and AIS have similar pathological conditions that are associated with small vessel disease (SVD) such as oxidative stress, inflammation, endothelial dysfunction, and neuronal injury. Therefore, it may be possible to find superior blood biomarkers of VaD among AIS blood biomarkers. Owing to recent developments, noncoding rnas such as microrna and long noncoding rna, which can be analyzed using a single drop of blood, are also particularly reliable VaD markers because they stably reflect brain tissue damage. A multimarker combining several blood biomarkers or artificial intelligence technology may also be beneficial to compensate for insufficiencies of a single blood biomarker. This review describes the blood biomarkers of VaD and how they are related to blood biomarkers of AIS.

关键词： Vascular dementia Acute ischemic stroke Biomarker noncoding rna Multimarker

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Dual role of the miR-146 family in rhinovirus-induced airway inflammation and allergic asthma exacerbation

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CLINICAL AND TRANSLATIONAL MEDICINE 2021年第6期11卷 e427页

作者： Laanesoo, Anet Urgard, Egon Periyasamy, Kapilraj Laan, Martti Bochkov, Yury A. Aab, Alar Magilnick, Nathaniel Pooga, Margus Gern, James E. Johnston, Sebastian L. Coquet, Jonathan M. Boldin, Mark P. Wengel, Jesper Altraja, Alan Bochenek, Grazyna Jakiela, Bogdan Rebane, Ana Univ Tartu Inst Biomed & Translat Med Ravila 14B EE-50414 Tartu Estonia Univ Wisconsin Sch Med & Publ Hlth Madison WI USA City Hope Natl Med Ctr Beckman Res Inst Dept Mol & Cellular Biol Duarte CA 91010 USA Univ Tartu Inst Technol Tartu Estonia Imperial Coll London Natl Heart & Lung Inst London England Imperial Coll Healthcare NHS Trust London England Karolinska Inst Dept Microbiol Tumor & Cell Biol MTC Stockholm Sweden Univ Southern Denmark Nucle Acid Ctr Dept Phys Chem & Pharm Odense Denmark Univ Tartu Dept Pulm Med Tartu Estonia Tartu Univ Hosp Lung Clin Tartu Estonia Jagiellonian Univ Med Coll Dept Med Krakow Poland

Rhinovirus (RV) infections are associated with asthma exacerbations. Microrna-146a and microrna-146b (miR-146a/b) are anti-inflammatory mirnas that suppress signaling through the nuclear factor kappa B (NF-kappa B) pathway and inhibit pro-inflammatory chemokine production in primary human bronchial epithelial cells (HBECs). In the current study, we aimed to explore whether miR-146a/b could regulate cellular responses to RVs in HBECs and airways during RV-induced asthma exacerbation. We demonstrated that expression of miR-146a/b and pro-inflammatory chemokines was increased in HBECs and mouse airways during RV infection. However, transfection with cell-penetrating peptide (CPP)-miR-146a nanocomplexes before infection with RV significantly reduced the expression of the pro-inflammatory chemokines CCL5, IL-8 and CXCL1, increased interferon-lambda production, and attenuated infection with the green fluorescent protein (GFP)-expressing RV-A16 in HBECs. Concordantly, compared to wild-type (wt) mice, Mir146a/b(-/-) mice exhibited more severe airway neutrophilia and increased T helper (Th)1 and Th17 cell infiltration in response to RV-A1b infection and a stronger Th17 response with a less prominent Th2 response in house dust mite extract (HDM)-induced allergic airway inflammation and RV-induced exacerbation models. Interestingly, intranasal administration of CPP-miR-146a nanocomplexes reduced HDM-induced allergic airway inflammation without a significant effect on the Th2/Th1/Th17 balance in wild-type mice. In conclusion, the overexpression of miR-146a has a strong anti-inflammatory effect on RV infection in HBECs and a mouse model of allergic airway inflammation, while a lack of miR-146a/b leads to attenuated type 2 cell responses in mouse models of allergic airway inflammation and RV-induced exacerbation of allergic airway inflammation. Furthermore, our data indicate that the application of CPP-miR-146a nanocomplexes has therapeutic potential for targeting airway inflamma

关键词： asthma bronchial epithelial cell house dust mite microrna neutrophils noncoding rna viral infection

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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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Identification and characterization of micrornas in the immature stage of the beneficial predatory bug Arma chinensis Fallou (Hemiptera: Pentatomidae)

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ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY 2021年第3期107卷 e21796-e21796页

作者： Yin, Yanfang Zhu, Yanjuan Mao, Jianjun Gundersen-Rindal, Dawn E. Liu, Chenxi Chinese Acad Agr Sci Inst Plant Protect Sino Amer Biol Control Lab Beijing 100193 Peoples R China USDA ARS Invas Insect Biocontrol & Behav Lab Beltsville MD USA

Micrornas (mirnas) are a type of small noncoding rnas that regulate gene expression at the posttranscriptional level and can influence significant biological processes. Arma chinensis (Hemiptera: Pentatomidae) is a predaceous insect species that preys upon a wide variety of insect pests. It is important to explore and understand the molecular mechanisms involving mirnas in regulating developmental and other gene expression for beneficial insects. However, examination of mirnas associated with Hemiptera, especially predatory bugs, has been absent or scarce. This study represents the first comprehensive analysis of predatory bug A. chinensis encoded mirnas through high throughput sequencing and predicts genes and biological processes regulated by the newly identified mirnas through analyzing their differential expression in and across five nymphal instars. A total of 64 A. chinensis mirnas, including 46 conserved mirnas and 18 novel mirnas, were identified by analysis of high throughput sequence reads mapped to the genome. A total of 2913 potential gene targets for these 64 mirnas were predicted by comprehensive analyses utilizing miRanda, PITA, and rnahybrid. Gene Ontology annotation of predicted target genes of A. chinensis suggested the key processes regulated by mirnas involved biological processes, regulation of cellular processes, and transporter activity. Kyoto Encyclopedia of Genes and Genomes pathway predictions included the Toll and Imd signaling pathway, Valine, leucine and isoleucine degradation, Steroid biosynthesis, the AGE-RAGE signaling pathway in diabetic complications, and Alanine, aspartate and glutamate metabolism. This newly identified mirnas through analyzing their differential expression, assessment of their predicted functions forms a foundation for further investigation of specific mirnas.

关键词： Arma chinensis development microrna noncoding rna nymph

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Low-bias ncrna libraries using ordered two-template relay: Serial template jumping by a modified retroelement reverse transcriptase

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2021年第42期118卷 e2107900118-e2107900118页

作者： Upton, Heather E. Ferguson, Lucas Temoche-Diaz, Morayma M. Liu, Xiao-Man Pimentel, Sydney C. Ingolia, Nicholas T. Schekman, Randy Collins, Kathleen Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA Univ Calif Berkeley Berkeley CA 94720 USA Univ Calif Berkeley Ctr Computat Biol Berkeley CA 94720 USA Univ Calif Berkeley Dept Plant & Microbial Biol Berkeley CA 94720 USA Univ Calif Berkeley HHMI Berkeley CA 94720 USA

Selfish, non-long terminal repeat (non-LTR) retroelements and mobile group II introns encode reverse transcriptases (RTs) that can initiate DNA synthesis without substantial base pairing of primer and template. Biochemical characterization of these enzymes has been limited by recombinant expression challenges, hampering understanding of their properties and the possible exploitation of their properties for research and biotechnology. We investigated the activities of representative RTs using a modified nonLTR RT from Bombyx mori and a group II intron RT from Eubacterium rectale. Only the non-LTR RT supported robust and serial template jumping, producing one complementary DNA (cDNA) from several templates each copied end to end. We also discovered an unexpected terminal deoxynucleotidyl transferase activity of the RTs that adds nucleotide(s) of choice to 3 ' ends of singleand/or double-stranded rna or DNA. Combining these two types of activity with additional insights about nontemplated nucleotide additions to duplexed cDNA product, we developed a streamlined protocol for fusion of next-generation sequencing adaptors to both cDNA ends in a single RT reaction. When benchmarked using a reference pool of micrornas (mirnas), library production by Ordered Two-Template Relay (OTTR) using recombinant non-LTR retroelement RT outperformed all commercially available kits and rivaled the low bias of technically demanding home-brew protocols. We applied OTTR to inventory rnas purified from extracellular vesicles, identifying mirnas as well as myriad other noncoding rnas (ncrnas) and ncrna fragments. Our results establish the utility of OTTR for automation-friendly, low-bias, end-to-end rna sequence inventories of complex ncrna samples.

关键词： non-LTR retroelement reverse transcriptase rna sequencing mirna trna noncoding rna

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NPI-GNN: Predicting ncrna-protein interactions with deep graph neural networks

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BRIEFINGS IN BIOINFORMATICS 2021年第5期22卷 bbab051-bbab051页

作者： Shen, Zi-Ang Luo, Tao Zhou, Yuan-Ke Yu, Han Du, Pu-Feng Tianjin Univ Coll Intelligence & Comp Tianjin 300350 Peoples R China

noncoding rnas (ncrnas) play crucial roles in many biological processes. Experimental methods for identifying ncrna-protein interactions (NPIs) are always costly and time-consuming. Many computational approaches have been developed as alternative ways. In this work, we collected five benchmarking datasets for predicting NPIs. Based on these datasets, we evaluated and compared the prediction performances of existing machine-learning based methods. Graph neural network (GNN) is a recently developed deep learning algorithm for link predictions on complex networks, which has never been applied in predicting NPIs. We constructed a GNN-based method, which is called noncoding rna-Protein Interaction prediction using Graph Neural Networks (NPI-GNN), to predict NPIs. The NPI-GNN method achieved comparable performance with state-of-the-art methods in a 5-fold cross-validation. In addition, it is capable of predicting novel interactions based on network information and sequence information. We also found that insufficient sequence information does not affect the NPI-GNN prediction performance much, which makes NPI-GNN more robust than other methods. As far as we can tell, NPI-GNN is the first end-to-end GNN predictor for predicting NPIs. All benchmarking datasets in this work and all source codes of the NPI-GNN method have been deposited with documents in a GitHub repo (https://***/AshuiRUA/NPI- GNN).

关键词： graph neural network ncrna-protein interaction noncoding rna

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Long noncoding rnas as biotargets in cisplatin-based drug resistance

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FUTURE ONCOLOGY 2018年第29期14卷 3085-3095页

作者： Abu, Nadiah Hon, Kha Wai Jeyaraman, Shivapriya Jamal, Rahman UKM Med Ctr UKM Med Mol Biol Inst UMBI Jalan Yaacob Latiff Kuala Lumpur 56000 Malaysia

Since its discovery, cisplatin has become the key drug in chemotherapy for cancers. Nevertheless, chemoresistance in cancers has become an impediment in using cisplatin for cancer treatment. The resistance toward cisplatin is multifaceted as it involves multiple cellular pathways. Ever since the knowledge of long noncoding rnas as modulators of various molecular pathways came to light, the interest in the biological function of lncrnas as biomarkers has increased dramatically. Numerous studies have reported the link between the dysregulation of lncrnas and drug resistance in cancers. More importantly, several lncrnas were found to be vital in regulating cisplatin resistance. Therefore, this review summarizes the recent efforts in linking between cisplatin resistance and different types of lncrnas.

关键词： biomarker cisplatin lncrna noncoding rna platinum

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MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small rna PinT

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CELL REPORTS 2021年第5期34卷 108722-108722页

作者： Santos, Sara Correia Bischler, Thorsten Westermann, Alexander J. Vogel, Joerg Univ Wurzburg Inst Mol Infect Biol Wurzburg Germany Univ Wurzburg Core Unit Syst Med Wurzburg Germany Helmholtz Ctr Infect Res Helmholtz Inst RNA Based Infect Res Wurzburg Germany

A full understanding of the contribution of small rnas (srnas) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated srna PinT, a known post-transcriptional timer of the two major virulence programs of Salmonella enterica. Using MS2 affinity purification and rna sequencing (MAPS), we identify PinT ligands in bacteria under in vitro conditions mimicking specific stages of the infection cycle and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression of steC mrna, eventually delaying actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator in Salmonella virulence and illustrate the need for complementary methods to reveal the full target suites of srnas.

关键词： MS2 affinity purification and rna-seq host-pathogen interaction infection noncoding rna post-transcriptional control PinT

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