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DEAH box rna helicase DHX38 associates with satellite I noncoding rna involved in chromosome segregation

GENES TO CELLS 2019年第8期24卷 585-590页

作者： Nishimura, Kanako Cho, Yukiko Tokunaga, Kazuaki Nakao, Mitsuyoshi Tani, Tokio Ideue, Takashi Kumamoto Univ Dept Biol Sci Grad Sch Sci & Technol Kumamoto Japan Inst Mol Embryol & Genet Dept Med Cell Biol Kumamoto Japan Kumamoto Univ Fac Adv Sci & Technol Kumamoto Japan

noncoding (nc) rna called satellite I is transcribed from the human centromere region. Depletion of this ncrna results in abnormal nuclear morphology because of defects in chromosome segregation. Some protein factors interact with this ncrna and function as a component of a nc ribonucleoprotein (RNP) complex in mitotic regulation. Here, we found that DHX38, a pre-mrna splicing-related DEAH box rna helicase, interacts with satellite I ncrna. Depletion of DHX38 resulted in defective chromosome segregation similar to knockdown of satellite I ncrna. Interaction between DHX38 and ncrna was interphase-specific, but DHX38 depletion affected the function of Aurora B, which associated with satellite I ncrna at mitotic phase. Based on these findings, we suggest that DHX38 has a role in mitotic regulation as a component of the satellite I ncRNP complex at interphase.

关键词： chromosome segregation noncoding rna ribonucleoprotein (RNP) complex

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Nuclear noncoding rna surveillance: is the end in sight?

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TRENDS IN GENETICS 2012年第7期28卷 306-313页

作者： Wolin, Sandra L. Sim, Soyeong Chen, Xinguo Yale Univ Sch Med Dept Cell Biol New Haven CT 06536 USA Yale Univ Sch Med Dept Mol Biophys & Biochem New Haven CT 06536 USA

Nuclear noncoding rna (ncrna) surveillance pathways play key roles in shaping the steady-state transcriptomes of eukaryotic cells. Defective and unneeded ncrnas are primarily degraded by exoribonucleases that rely on protein cofactors to identify these rnas. Recent studies have begun to elucidate both the mechanisms by which these cofactors recognize aberrant rnas and the features that mark rnas for degradation. One crucial rna determinant is the presence of an accessible end;in addition, the failure of aberrant rnas to fold into compact structures and assemble with specific binding proteins probably also contributes to their recognition and subsequent degradation. To date, ncrna surveillance has been most extensively studied in budding yeast. However, mammalian cells possess nucleases and cofactors that have no known yeast counterparts, indicating that rna surveillance pathways may be more complex in metazoans. Importantly, there is evidence that the failure of ncrna surveillance pathways contributes to human disease.

关键词： noncoding rna quality control rna degradation oligoadenylation TRAMP complex exoribonucleases

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Long noncoding rna HOTAIR involvement in cancer

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TUMOR BIOLOGY 2014年第10期35卷 9531-9538页

作者： Wu, Yansheng Zhang, Li Wang, Yang Li, Hui Ren, Xiubao Wei, Feng Yu, Wenwen Wang, Xudong Zhang, Lun Yu, Jinpu Hao, Xishan Tianjin Med Univ Canc Inst & Hosp Dept Maxillofacial & Otorhinolaryngol Head & Neck Tianjin Peoples R China Tianjin Med Univ Canc Inst & Hosp Dept Immunol Tianjin Peoples R China Tianjin Med Univ Canc Inst & Hosp Biotherapy Ctr Tianjin Peoples R China Natl Clin Res Ctr Canc Key Lab Canc Prevent & Therapy Tianjin Peoples R China Key Lab Canc Immunol & Biotherapy Tianjin Peoples R China Tianjin Med Univ Canc Inst & Hosp Dept Breast Canc Med Oncol Tianjin Peoples R China Key Lab Canc Prevent & Therapy Tianjin Peoples R China

Evidences have been provided that long noncoding rnas (lncrnas) act as key molecules in epigenetic regulation and are involved in the development process of cancer in recent studies. HOX transcript antisense rna (HOTAIR), a long intergenic noncoding rna (lincrna), functions as a molecular scaffold to link and target two histone modification complexes PRC2 and LSD1, then reprograms chromatin states by couples histone H3K27 methylation and H3K4 demethylation for epigenetic gene silencing to promote cancer metastasis. HOTAIR, regarded as an oncogene, is pervasively overexpressed inmost solid cancers and correlated with tumor invasion, progression, metastasis, and poor prognosis, and HOTAIR has been proven to play a critical role in most biological process of cancer and would be a potential new target in cancer therapy.

关键词： noncoding rna HOTAIR Cancer Metastasis Gene regulation

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Maintenance of epigenetic information: a noncoding rna perspective

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CHROMOSOME RESEARCH 2013年第6-7期21卷 615-625页

作者： Mondal, Tanmoy Kanduri, Chandrasekhar Gothenburg Univ Sahlgrenska Acad Inst Biomed Dept Med Genet S-40530 Gothenburg Sweden

Along the lines of established players like chromatin modifiers and transcription factors, noncoding rna (ncrna) are now widely accepted as one of the key regulatory molecules in epigenetic regulation of transcription. With increasing evidence of ncrnas in the establishment of gene silencing through their ability to interact with major chromatin modifiers, in the current review, we discuss their prospective role in the area of inheritance and maintenance of these established silenced states which can be reversible or irreversible in nature. In addition, we attempt to understand and speculate how these rna dependent or independent maintenance mechanisms differ between each other in a developmental stage, tissue, and gene-specific manner in different biological contexts by utilizing known/unknown regulatory factors.

关键词： noncoding rna Long noncoding rna Chromatin Histone modifications DNA methylation Genomic imprinting X chromosome inactivation Kcnq1ot1 Xist Replication PRC1 PRC2

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A long noncoding rna influences the choice of the X chromosome to be inactivated

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2022年第28期119卷 e2118182119-e2118182119页

作者： Hierholzer, Andreas Chureau, Corinne Liverziani, Alessandra Ruiz, Nerea Blanes Cattanach, Bruce M. Young, Alexander N. Kumar, Manish Cerase, Andrea Avner, Phil EMBL Rome Epigenet & Neurobiol Unit I-00015 Monterotondo Italy Inst Pasteur Dev & Stem Cell Biol Dept Genom & Epigen Anim Dev F-75015 Paris France Queen Mary Univ London Barts & London Sch Med & Dent Blizard Inst London E1 2AT England MRC Harwell Mammalian Genet Unit Didcot OX11 0RD Berks England Swiss Fed Inst Technol Dept Biosyst Sci & Engn CH-4058 Basel Switzerland Augusta Univ Med Coll Georgia Dept Neurosurg Augusta GA 30912 USA

X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element (Xce). Although the Xce was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding rna (lncrna) within the Xce locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong Xce alleles we show that Lppnx modulates the expression of Xist lncrna, one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of Xist. This effect is counteracted by enhanced binding of Rex1 in DxPas34, another key element in XCI regulating the activity of Tsix lncrna, the main antagonist of Xist, in the strong but not in the weak Xce allele. These results suggest that the different susceptibility for XCI observed in weak and strong Xce alleles results from differential transcription factor binding of Xist Intron 1 and DxPas34, and that Lppnx represents a decisive factor in explaining the action of the Xce.

关键词： X chromosome inactivation X-controlling element pluripotency factors female mouse embryo noncoding rna

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T cell activation induces a noncoding rna transcript sensitive to inhibition by immunosuppressant drugs and encoded by the proto-oncogene, BIC

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CELLULAR IMMUNOLOGY 2002年第1-2期217卷 78-86页

作者： Haasch, D Chen, YW Reilly, RM Chiou, XG Koterski, S Smith, ML Kroeger, P McWeeny, K Halbert, DN Mollison, KW Djuric, SW Trevillyan, JM Abbott Labs Global Pharmaceut Res & Dev Abbott Pk IL 60064 USA

In a search for novel early T cell activation transcripts, we identified expressed sequence tags (ESTs) more abundantly expressed in normal human CD4(+) T lymphocytes fully activated by a 5 h exposure to CD3 plus CD28 mAbs, compared to the same cells stimulated with either CD3 mAb or CD28 mAb alone. An EST was identified that hybridized with a 1.7 kb transcript expressed in activated T cells but was undetectable by Northern blot analysis in resting T cells or other normal tissues, The T cell transcript was maximally induced within 6 h and remained elevated for at least 47 h. Induction of the transcript was blocked by cyclosporin A, FK506, and dexamethasone but not by rapamycin. The transcript was polyadenylated but lacked an open reading. A BLAST search of the NCBI database revealed that the transcript shared identity with the recently reported human BICproto-oncogene that encodes a noncoding mrna(W. Tam, Gene 274 (2001) 157). Our data demonstrate that transcriptional activation of the BIC protooncogene is an early and sustained T cell activation event and suggest an important role for noncoding mrna in T cell function. (C) 2002 Elsevier Science (USA) All rights reserved.

关键词： noncoding rna proto-oncogene T cell activation immunosuppressant drug

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Comprehensive analysis of long noncoding rna and mrna expression patterns in sheep testicular maturation

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BIOLOGY OF REPRODUCTION 2018年第3期99卷 650-661页

作者： Yang, Hua Wang, Feng Li, Fengzhe Ren, Caifang Pang, Jing Wan, Yongjie Wang, Ziyu Feng, Xu Zhang, Yanli Nanjing Agr Univ Coll Anim Sci & Technol Jiangsu Livestock Embryo Engn Lab 1 Weigang Nanjing 210095 Jiangsu Peoples R China

Long noncoding rnas (Lncrnas) have been identified as important regulators of testis development;however, their expression patterns and roles in sheep are not yet clear. Thus, we used stranded specific rna-seq to profile the testis transcriptome (lncrnas and mrnas) in premature and mature sheep. Hormone levels and the testis index were examined, and histological analyses were performed at five stages of testis development, 5-day-old (D5), 3-month-old (3M), 6-month-old (6M), 9-month-old (9M), and 2-year-old (2Y), the results of which indicate a significant difference in hormone levels and testis morphometries between the 3M and 9M stages (P < 0.05). Based on the comparison between 3M and 9M samples, we found 1,118 differentially expressed (DE) lncrnas and 7,253 DE mrnas in the testes, and qRT-PCR analysis showed that the results correlated well with the transcriptome data. Furthermore, we constructed lncrna-protein-coding gene interaction networks. Forty-seven DE lncrna-targeted genes enriched for male reproduction were obtained by cis- and trans-acting;51 DE lncrnas and 45 cis-targets, 2 DE lncrnas and 2 trans-targets were involved in this network. Of these, 5 lncrnas and their targets, PRKCD, NANOS3, SERPINA5, and CYP19A1, were enriched for spermatogenesis and male gonad development signaling pathways. We further examined the expression levels of 5 candidate lncrnas and their target genes during testis development. Lastly, the interaction of lncrna TCONS_00863147 and its target gene PRKCD was validated in vitro in sheep Leydig cells. This study provides a valuable resource for further study of lncrna function in sheep testis development and spermatogenesis. Summary Sentence The lncrna profiles during Sheep testicular maturation.

关键词： noncoding rna sheep testis Leydig cells

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Novel brain-expressed noncoding rna, HSTR1, identified at a human-specific variable number tandem repeat locus with a human accelerated region

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2018年第3期503卷 1478-1483页

作者： Suzuki, Shunsuke Miyabe, Emi Inagaki, Shun Shinshu Univ Grad Sch Sci & Technol Dept Agr 8304 Minami Minowa Kami Ina Nagano 3994598 Japan Shinshu Univ ICCER Inst Biomed Sci Dept Interdisciplinary Genome Sci & Cell Metab 8304 Minami Minowa Kami Ina Nagano 3994598 Japan

The evolutionary conserved genomic sequences that have acquired significantly increased number of nucleotide substitutions specifically in the human lineage, called human accelerated regions (HARs), have been identified as candidate genomic regions that have contributed to the evolution of human-specific traits. A number of HARs were indeed shown to have novel enhancer activity and be associated with human-specific brain development and with cognition and social behavior. It is therefore of great importance to investigate the details of genomic function of each HAR to understand the roles of HARs as critical contributors to the genetic basis of human evolution. In this study, we identified a previously unannotated brain-expressed noncoding rna gene, HSTR1, at a human-specific tandem repeat locus. Notably, the 5' flanking sequence of HSTR1 showed the signature of HARs and the dramatic human-specific enhancement of promoter activity, providing the evidence of positive selection to increase the expression level of HSTR1 during human evolution. We also revealed that the tandem repeat number in HSTR1 was highly variable among individual alleles and affected the stability of HSTR1 rna, suggesting variation in the activity of HSTR1 between human individuals. Our work thus provides a novel candidate gene that potentially contributed to the evolution of the human brain. It may also underpin some of the variation between human brains. (C) 2018 Elsevier Inc. All rights reserved.

关键词： noncoding rna Tandem repeat Human accelerated region Brain evolution

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The Long noncoding rna Transcriptome of Dictyostelium discoideum Development

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G3-GENES GENOMES GENETICS 2017年第2期7卷 387-398页

作者： Rosengarten, Rafael D. Santhanam, Balaji Kokosar, Janez Shaulsky, Gad Baylor Coll Med Dept Mol & Human Genet BCM Smith Med Res BldgMail Stop BCM225 Houston TX 77030 USA Baylor Coll Med Computat & Integrat Biomed Res Ctr Houston TX 77030 USA

Dictyostelium discoideum live in the soil as single cells, engulfing bacteria and growing vegetatively. Upon starvation, tens of thousands of amoebae enter a developmental program that includes aggregation, multicellular differentiation, and sporulation. Major shifts across the protein-coding transcriptome accompany these developmental changes. However, no study has presented a global survey of long noncoding rnas (ncrnas) in D. discoideum. To characterize the antisense and long intergenic noncoding rna (lncrna) transcriptome, we analyzed previously published developmental time course samples using an rna-sequencing (rna-seq) library preparation method that selectively depletes ribosomal rnas (rrnas). We detected the accumulation of transcripts for 9833 protein-coding messenger rnas (mrnas), 621 lncrnas, and 162 putative antisense rnas (asrnas). The noncoding rnas were interspersed throughout the genome, and were distinct in expression level, length, and nucleotide composition. The noncoding transcriptome displayed a temporal profile similar to the coding transcriptome, with stages of gradual change interspersed with larger leaps. The transcription profiles of some noncoding rnas were strongly correlated with known differentially expressed coding rnas, hinting at a functional role for these molecules during development. Examining the mitochondrial transcriptome, we modeled two novel antisense transcripts. We applied yet another ribosomal depletion method to a subset of the samples to better retain transfer rna (trna) transcripts. We observed polymorphisms in trna anticodons that suggested a post-transcriptional means by which D. discoideum compensates for codons missing in the genomic complement of trnas. We concluded that the prevalence and characteristics of long ncrnas indicate that these molecules are relevant to the progression of molecular and cellular phenotypes during development.

关键词： transcriptome time course development noncoding rna ribosomal rna depletion Dictyostelium discoideum slime mold

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Long noncoding rna-Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary Hypertension

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MOLECULAR THERAPY 2019年第12期27卷 2166-2181页

作者： Xing, Yan Zheng, Xiaodong Fu, Yao Qi, Jing Li, Minghui Ma, Mingfei Wang, Shuang Li, Shuzhen Zhu, Daling Harbin Med Univ Daqing Dept Pharmacol Daqing 163319 Heilongjiang Peoples R China Harbin Med Univ Daqing Dept Genet & Cell Biol Daqing 163319 Heilongjiang Peoples R China Harbin Med Univ Coll Pharm Harbin 150081 Heilongjiang Peoples R China Harbin Med Univ Daqing Dept Pharmaceut Daqing 163319 Heilongjiang Peoples R China Harbin Med Univ Coll Pharm Dept Biopharmaceut Sci Harbin 150086 Heilongjiang Peoples R China Harbin Med Univ Daqing Cent Lab Daqing 163319 Peoples R China State Prov Key Labs Biomed Pharmaceut China Daqing 163319 Peoples R China Harbin Med Univ Minist Educ Key Lab Cardiovasc Med Res Harbin 150081 Heilongjiang Peoples R China

The expression and function of long noncoding rnas (lncrnas) in the development of hypoxic pulmonary hypertension (HPH), especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs), are largely unknown. Herein, we examined the expression and role of lncrna-maternally expressed gene 3 (lncrna-MEG3) in HPH. lncrna-MEG3 was significantly increased and primarily localized in the cytoplasm of hypoxic PASMCs. lncrna-MEG3 knockdown by lung-specific delivery of small interfering rnas (sirnas) significantly inhibited the development of HPH in vivo. Silencing of lncrna-MEG3 by sirnas and gapmers attenuated proliferation and cell-cycle progression in both PASMCs from idiopathic pulmonary arterial hypertension (iPAH) patients (iPAH-PASMCs) and hypoxia-exposed PASMCs in vitro. Mechanistically, we found that lncrna-MEG3 interacts with and leads to the degradation of microrna-328-3p (miR-3283p), leading to upregulation of insulin-like growth factor 1 receptor (IGF1R). Additionally, higher expression of lncrnaMEG3 and IGF1R and lower expression of miR-328-3p were observed in iPAH-PASMCs and relevant HPH models. These data provide insights into the contribution of lncrna-MEG3 to HPH. Upregulation of lncrna-MEG3 sequesters cytoplasmic miR-328-3p, eventually leading to expression of IGF1R, revealing a regulatory mechanism by lncrnas in hypoxia-induced PASMC proliferation.

关键词： noncoding rna maternally expressed gene 3 hypoxic pulmonary hypertension proliferation microrna-328 insulin-like growth factor 1 receptor

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