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rna in Human Sperm and Some Problems of Male Fertility

RUSSIAN JOUrnaL OF GENETICS 2018年第12期54卷 1410-1415页

作者： Mazilina, M. A. Komarova, E. M. Baranov, V. S. Ott Res Inst Obstet Gynecol & Reproductol St Petersburg 199034 Russia St Petersburg State Univ Dept Genet & Biotechnol St Petersburg 199034 Russia

The progress of genomic technologies has led to an increased understanding of the role of spermatozoa and spermioplasm rna complex which is associated with male fertility. In this review, information about functional role of spermatozoal rna such as messenger rna and different types of noncoding rnas is discussed. Data on the relationship between specific noncoding sperm rnas and male infertility, oocyte fertilization, and early embryo development are discussed. The potential role of sperm rnas as a predictor of outcome of assisted reproductive technologies (ART) is highlighted. Accumulation and processing of data on a unique rna pattern in human spermatozoa will improve the algorithm for examining infertile couples, make it possible to increase the efficiency of ART, and help to choose the best way to overcome infertility.

关键词： human sperm sperm rna noncoding rna microrna male infertility assisted reproductive technologies

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Repression of Divergent noncoding Transcription by a Sequence-Specific Transcription Factor

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MOLECULAR CELL 2018年第6期72卷 942-+页

作者： Wu, Andrew C. K. Patel, Harshil Chia, Minghao Moretto, Fabien Frith, David Snijders, Ambrosius P. van Werven, Folkert J. Francis Crick Inst Cell Fate & Gene Regulat Lab 1 Midland Rd London NW1 1AT England Francis Crick Inst Bioinformat & Biostat 1 Midland Rd London NW1 1AT England Francis Crick Inst Prot Anal & Prote Platform 1 Midland Rd London NW1 1AT England

Many active eukaryotic gene promoters exhibit divergent noncoding transcription, but the mechanisms restricting expression of these transcripts are not well understood. Here, we demonstrate how a sequence-specific transcription factor represses divergent noncoding transcription at highly expressed genes in yeast. We find that depletion of the transcription factor Rap1 induces noncoding transcription in a large fraction of Rap1-regulated gene promoters. Specifically, Rap1 prevents transcription initiation at cryptic promoters near its binding sites, which is uncoupled from transcription regulation in the protein-coding direction. We further provide evidence that Rap1 acts independently of previously described chromatin-based mechanisms to repress cryptic or divergent transcription. Finally, we show that divergent transcription in the absence of Rap1 is elicited by the RSC chromatin remodeler. We propose that a sequence-specific transcription factor limits access of basal transcription machinery to regulatory elements and adjacent sequences that act as divergent cryptic promoters, thereby providing directionality toward productive transcription.

关键词： yeast RSC promoter Rap1 transcription divergent noncoding rna transcription factor repression directionality

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Microrna-125b Promotes Hepatic Stellate Cell Activation and Liver Fibrosis by Activating RhoA Signaling

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MOLECULAR THERAPY-NUCLEIC ACIDS 2018年 12卷 57-66页

作者： You, Kai Li, Song-Yang Gong, Jiao Fang, Jian-Hong Zhang, Chong Zhang, Min Yuan, Yunfei Yang, Jine Zhuang, Shi-Mei Sun Yat Sen Univ Sch Life Sci Collaborat Innovat Ctr Canc Med Key Lab Gene EngnMinist EducState Key Lab Bioco Guangzhou Guangdong Peoples R China Sun Yat Sen Univ Affiliated Hosp 3 Key Lab Liver Dis Guangdong Prov Guangzhou Guangdong Peoples R China Sun Yat Sen Univ Canc Ctr Guangzhou Guangdong Peoples R China

miR-125b is frequently dysregulated in different diseases. Activation of hepatic stellate cells (HSCs) is a critical event during liver fibrogenesis. However, the function and its underlying mechanism of miR-125b in HSC activation and liver fibrosis are still unknown. Here, we showed that miR-125b was upregulated in HSCs, but not in hepatocytes, during hepatic fibrogenesis in vivo and upon culture activation in vitro. Inhibition of miR-125b suppressed the expression of profibrogenic genes in culture-activated primary HSCs and reduced the basal and transforming growth factor beta (TGF-beta)-induced alpha-smooth muscle actin (alpha-SMA) expression and cell contraction of the immortalized HSC cell line. In contrast, ectopic expression of miR-125b promoted a-SMA expression and HSC contraction. Moreover, antagonizing miR-125b in vivo significantly alleviated liver fibrosis in CCl4-treated mice. Mechanistically, overexpression of miR-125b in HSCs enhanced RhoA activity by directly targeting StAR-related lipid transfer (START) domain containing 13 (Stard13), a RhoA-specific GTPase-activating protein, whereas knockdown of miR-125b abrogated RhoA activation. Furthermore, inhibition of RhoA or its downstream molecules, Mrtf-A and Srf, attenuated the miR-125b-induced alpha-SMA expression and HSC contraction. Therefore, our findings identify a miR-125b-Stard13-RhoA-alpha-SMA signaling cascade in HSCs and highlight its importance in hepatic fibrosis.

关键词： noncoding rna microrna-125b Stard13 RhoA signaling hepatic stellate cell liver fibrosis

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Divergent evolution in the genomes of closely related lacertids, Lacerta viridis and L. bilineata, and implications for speciation

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GIGASCIENCE 2019年第2期8卷 giy160页

作者： Kolora, Sree Rohit Raj Weigert, Anne Saffari, Amin Kehr, Stephanie Walter Costa, Maria Beatriz Sproeer, Cathrin Indrischek, Henrike Chintalapati, Manjusha Lohse, Konrad Doose, Gero Overmann, Joerg Bunk, Boyke Bleidorn, Christoph Grimm-Seyfarth, Annegret Henle, Klaus Nowick, Katja Faria, Rui Stadler, Peter F. Schlegel, Martin German Ctr Integrat Biodivers Res iDiv Deutsch Pl 5e D-04103 Leipzig Germany Univ Leipzig Dept Comp Sci Bioinformat Grp Hartelstr 16-18 D-04107 Leipzig Germany Univ Leipzig Interdisciplinary Ctr Bioinformat Hartelstr 16-18 D-04107 Leipzig Germany Univ Leipzig Inst Biol Mol Evolut & Systemat Anim Talstr 33 D-04103 Leipzig Germany Max Planck Inst Evolutionary Anthropol Deutsch Pl 6 D-04103 Leipzig Germany Free Univ Berlin Dept Biol Chem & Pharm Inst Zool Human Biol Grp Konigin Luise Str 1-3 D-14195 Berlin Germany Embrapa Agroenergia Parque Estacaeo Biol PqEB BR-70770901 Brasilia DF Brazil Leibniz Inst DSMZ German Collect Microorganisms & Dept Microbial Ecol & Divers Res Inhoffenstr 7B D-38124 Braunschweig Germany Max Planck Inst Mol Cell Biol & Genet Pfotenhauerstr 108 D-01307 Dresden Germany Max Planck Inst Phys Komplexer Syst Noethnitzerstr 38 D-01187 Dresden Germany Ctr Syst Biol Dresden Pfotenhauerstr 108 D-01397 Dresden Germany Univ Edinburgh Inst Evolutionary Biol Kings BldgCharlotte Auerbach Rd Edinburgh EH9 3FL Midlothian Scotland Univ Gottingen Dept Anim Evolut & Biodivers Untere Karspule 2 D-37073 Gottingen Germany CSIC Museo Nacl Hist Nat Madrid 28006 Spain UFZ Helmholtz Ctr Environm Res Dept Conservat Biol Permoserstr 15 D-04318 Leipzig Germany Univ Potsdam Plant Ecol & Nat Conservat Muhlenberg 3 D-14476 Potsdam Germany Univ Sheffield Dept Anim & Plant Sci Alfred BldgWestern Bank Sheffield S10 2TN S Yorkshire England Univ Leipzig Competence Ctr Scalable Data Serv & Solut Dresden Augustuspl 12 D-04107 Leipzig Germany Max Planck Inst Math Sci Inselstr 22 D-04103 Leipzig Germany Fraunhofer Inst Zelltherapie & Immunol Perlickstr 1 D-04103 Leipzig Germany Univ Vienna Dept Theoret Chem Wahringer Str 17 A-1090 Vienna Austria Univ Copenhagen Ctr Noncoding RNA Technol & Hlth Gronnegardsvej 3 DK-1870 Frederiksberg C Denmark Santa Fe Inst 1399 Hyde Pk Rd Santa Fe NM 87501 USA

Background Lacerta viridis and Lacerta bilineata are sister species of European green lizards (eastern and western clades, respectively) that, until recently, were grouped together as the L. viridis complex. Genetic incompatibilities were observed between lacertid populations through crossing experiments, which led to the delineation of two separate species within the L. viridis complex. The population history of these sister species and processes driving divergence are unknown. We constructed the first high-quality de novo genome assemblies for both L. viridis and L. bilineata through Illumina and PacBio sequencing, with annotation support provided from transcriptome sequencing of several tissues. To estimate gene flow between the two species and identify factors involved in reproductive isolation, we studied their evolutionary history, identified genomic rearrangements, detected signatures of selection on non-coding rna, and on protein-coding genes. Findings Here we show that gene flow was primarily unidirectional from L. bilineata to L. viridis after their split at least 1.15 million years ago. We detected positive selection of the non-coding repertoire;mutations in transcription factors;accumulation of divergence through inversions;selection on genes involved in neural development, reproduction, and behavior, as well as in ultraviolet-response, possibly driven by sexual selection, whose contribution to reproductive isolation between these lacertid species needs to be further evaluated. Conclusion The combination of short and long sequence reads resulted in one of the most complete lizard genome assemblies. The characterization of a diverse array of genomic features provided valuable insights into the demographic history of divergence among European green lizards, as well as key species differences, some of which are candidates that could have played a role in speciation. In addition, our study generated valuable genomic resources that can be used to address cons

关键词： sister species PacBio and Illumina de novo hybrid assembly transcripts noncoding rna zinc fingers positive selection UV response inversions gene flow

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Genomewide analysis of circular rna in pituitaries of normal and heat-stressed sows

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BMC GENOMICS 2019年第1期20卷 1013-1013页

作者： Zhang, Haojie Hu, Baoyu Xiong, Jiali Chen, Ting Xi, Qianyun Luo, Junyi Jiang, Qingyan Sun, Jiajie Zhang, Yongliang South China Agr Univ Guangdong Prov Key Lab Anim Nutrit Regulat Natl Engn Res Ctr Breeding Swine Ind Coll Anim Sci Wushan Rd Guangzhou 510642 Guangdong Peoples R China

Background: As a newly characterized type of noncoding rna, circular rna (circrna) has been shown to have functions in diverse biological processes of animals. It has been reported that several noncoding rnas may regulate animals' response to heat stress which can be easily induced by hyperthermia in summer. However, the expression and functions of circrnas in the pituitary of sows and whether they participate in heat stress adaption are still unclear. Results: In this study, we found that high temperature over the thermoneutral zone of sows during the summer increased the serum heat shock protein 70 (HSP70) level, decreased the superoxide dismutase (SOD) vitality and prolactin (PRL) concentration, and induced heat stress in sows. Then, we explored circrna in the pituitary of heat-stressed and normal sows using rna sequencing and bioinformatics analysis. In total, 12,035 circrnas were detected, with 59 circrnas differentially expressed, including 42 up-regulated and 17 down-regulated circrnas in pituitaries of the heat-stressed sows. Six randomly selected circrnas were identified through reverse transcription PCR followed by DNA sequencing and other 7 randomly selected differentially expressed circrnas were verified by quantitative real-time PCR analysis. The predicted target genes regulated by circrnas through sponging micrornas (mirnas) were enriched in metabolic pathway. Furthermore, the predicted circrna-mirna-mrna interactions showed that some circrnas might sponge mirnas to regulate pituitary-specific genes and heat shock protein family members, indicating circrna's roles in pituitary hormone secretion and heat stress response. Conclusions: Our results provided a meaningful reference to understand the functions of circrna in the porcine pituitary and the mechanisms by which circrna may participate in animals' response to heat stress.

关键词： Hyperthermia noncoding rna Pituitary Profiling Sows

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mirna regulates noncoding rna: a noncanonical function model

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TRENDS IN BIOCHEMICAL SCIENCES 2012年第11期37卷 457-459页

作者： Chen, Xi Liang, Hongwei Zhang, Chen-Yu Zen, Ke Nanjing Univ Sch Life Sci State Key Lab Pharmaceut Biotechnol Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol Nanjing 210093 Jiangsu Peoples R China

It has long been assumed that mirnas can only target protein-coding mrnas in the cytoplasm. Recent studies, however, reveal mirnas are also transported from the cytoplasm to the nucleus, where they function in a nonca... 详细信息

关键词： mirna noncoding rna nucleus Argonaute exportin importin

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Measurement of Urinary Level of a Specific Competing endogenous rna network (FOS and RCAN mrna/ miR-324-5p, miR-4738-3p, /lncrna miR-497-HG) Enables Diagnosis of Bladder Cancer

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UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 2019年第4期37卷 292.e19-292.e27页

作者： Eissa, Sanaa Safwat, Maheera Matboli, Marwa Zaghloul, Ashraf El-Sawalhi, Maha Shaheen, Amira Ain Shams Univ Res Inst MASRI Fac Med Med Biochem & Mol Biol Dept Cairo 11381 Egypt Cairo Univ Fac Pharm Biochem Dept Kasr El Aini St Cairo 11562 Egypt Cairo Univ Natl Canc Inst Dept Surg Oncol Cairo Egypt

Objective: To assist in the diagnosis, treatment, and prognostic prediction of bladder cancer, the molecular patterns associated with it should be elucidated. Competing endogenous rna network: Microrna (mirna), long noncoding rna (lncrna), and their target autophagy genes have been strongly implicated in tumor development and metastasis. Patients and methods: Bioinformatics analysis was performed to retrieve a cerna: lncrna-mirna-mrna network linked to autophagy and relevant to bladder cancer. Expression of selected noncoding human rnas (miR-324-5p, miR-4738-3p, and lncrna miR-497-HG) and their target genes (RCAN1 mrna and FOSB mrna) was examined by qPCR in bladder tissues and urine samples obtained from 196 individuals (98 patients with bladder cancer, 48 patients with benign lesions, and 50 healthy controls). Results: Expression levels of the selected genes in urine samples in the bladder cancer group were significantly different from those in the control group (P < 0.001). Expression in bladder cancer tissue samples correlated with that in urine samples. Urinary expression levels of all biomarkers had high accuracy to distinguish patients with and without bladder cancer, with FOSB mrna and RCAN1 mrna having the highest accuracy (99% for RCAN1 mrna or FOSB mrna, 87.8% for miR-324-5p, 84.7% for miR-4738-3p, and 90.5% for lncrna miR-497-HG). FOSB mrna and RCAN1 mrna expression showed also a higher accuracy than cytology (77.6%). Conclusion: The significant differential expression of the cerna network: lncrna-mirna-mrna network in bladder cancer as compared to noncancerous controls has revealed the superior accuracy of the chosen biomarkers to cytology, especially FOSB mrna and RCAN1 mrna, suggesting their involvement in bladder cancer pathogenesis and promising role for future diagnosis, and targeted therapy. (C) 2019 Elsevier Inc. All rights reserved.

关键词： Bladder cancer Autophagy Urine cytology noncoding rna Urinary biomarkers

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Biology and clinical relevance of noncoding sno/scarnas

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TRENDS IN CARDIOVASCULAR MEDICINE 2018年第2期28卷 81-90页

作者： Cao, Thuy Rajasingh, Sheeja Samanta, Saheli Dawn, Buddhadeb Bittel, Douglas C. Rajasingh, Johnson Cardiovasc Res Inst Dept Internal Med Div Cardiovasc Dis Kansas City KS USA Childrens Mercy Hosp Kansas City MO 64108 USA Univ Kansas Med Ctr Dept Biochem & Mol Biol Kansas City KS 66160 USA

Small nucleolar rnas (snornas) are a group of noncoding rnas that perform various biological functions, including biochemical modifications of other rnas, precursors of mirna, splicing, and telomerase activity. The small Cajal body-associated rnas (scarnas) are a subset of the snorna family and collect in the Cajal body where they perform their canonical function to biochemically modify spliceosomal rnas prior to maturation. Failure of sno/scarnas have been implicated in pathology such as congenital heart anomalies, neuromuscular disorders, and various malignancies. Thus, understanding of sno/scarnas demonstrates the clinical value.

关键词： noncoding rna Small Cajal body-associated rna Spliceosomal rna Small nucleolar rna Alternative splicing

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The Major rna-Binding Protein ProQ Impacts Virulence Gene Expression in Salmonella enterica Serovar Typhimurium

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MBIO 2019年第1期10卷 e02504-18页

作者： Westermann, Alexander J. Venturini, Elisa Sellin, Mikael E. Foerstner, Konrad U. Hardt, Wolf-Dietrich Vogel, Joerg Helmholtz Inst RNA Based Infect Res HIRI Wurzburg Germany Univ Wurzburg IMIB Wurzburg Germany Univ Wurzburg Core Unit Syst Med Wurzburg Germany Swiss Fed Inst Technol Inst Microbiol Zurich Switzerland

FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major rna-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mrnas from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual rna-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major rna chaperone in Salmonella, Hfq, reinforces the notion that these two global rna-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding rnas (srnas), we show that the 3' UTR-derived srna STnc540 is capable of repressing an infection-induced magnesium transporter mrna in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of rna-binding proteins in regulating bacterial virulence programs. IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked "third domain" of small rna-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this rna-binding protein compare with those of Hfq, another central protein in rna-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover,

关键词： Hfq noncoding rna ProQ rna-seq bacterial pathogen posttranscriptional control

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Expressional activation and functional roles of human endogenous retroviruses in cancers

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REVIEWS IN MEDICAL VIROLOGY 2019年第2期29卷 e2025-e2025页

作者： Zhang, Mengwen Liang, Jessie Qiaoyi Zheng, Shu Zhejiang Univ Dept Plast & Reconstruct Surg Affiliated Hosp 2 Sch Med Hangzhou Zhejiang Peoples R China Chinese Univ Hong Kong Inst Digest Dis Hong Kong Peoples R China Chinese Univ Hong Kong Li Ka Shing Inst Hlth Sci State Key Lab Digest Dis Dept Med & TherapeutCUHK Shenzhen Res Inst Hong Kong Peoples R China Zhejiang Univ Canc Inst Affiliated Hosp 2 Sch Med Hangzhou Zhejiang Peoples R China Zhejiang Univ Minist Educ Key Lab Canc Prevent & Intervent Hangzhou Zhejiang Peoples R China Zhejiang Univ Dept Surg Oncol Affiliated Hosp 2 Sch Med Hangzhou Zhejiang Peoples R China

Human endogenous retroviruses (HERVs) are widely believed to be remnants of ancestral germ line infections by exogenous retroviruses. Although HERVs are deemed as "nonfunctional DNAs" due to loss of most of their viral protein coding capacity during evolution as part of the human genome, cumulative evidences are showing the expressional activation and potential roles of HERVs in diseases especially cancers. Work by other researchers and us has observed the dysregulation of HERVs in cancers, identified new HERV-related genes, and revealed their potential importance in cancer development. Here, we summarized the current knowledge on the mechanisms of the expressional activation and functional roles of HERVs, with a focus on the H family HERV (HERV-H), in carcinogenesis. HERV expression is regulated by external chemical or physical substances and exogenous virus infection, as well as host factors such as epigenetic DNA methylation, transcription factors, cytokines, and small rnas. Diverse roles of HERVs have been proposed by acting in the forms of noncoding rnas, proteins, and transcriptional regulators during carcinogenesis. However, much remains to be learnt about the contributions of HERVs to human cancers. More investigation is warranted to elucidate the functions of these "fossil remnants" yet important viral DNAs in the human genome.

关键词： aberrant expression cancer human endogenous retrovirus (HERV) long terminal repeat (LTR) noncoding rna

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