scispace - formally typeset
Search or ask a question
Journal ArticleDOI

NEAT1 Long Noncoding RNA and Paraspeckle Bodies Modulate HIV-1 Posttranscriptional Expression

01 Mar 2013-Mbio (American Society for Microbiology)-Vol. 4, Iss: 1
TL;DR: The knockdown of NEAT1 enhances virus production through increased nucleus-to-cytoplasm export of Rev-dependent instability element (INS)-containing HIV-1 mRNAs as well as identifying the nuclear paraspeckle body as another important subcellular organelle for HIV- 1 replication.
Abstract: Most of the human genome is transcribed into protein-noncoding RNAs (ncRNAs), including small ncRNAs and long ncRNAs (lncRNAs). Over the past decade, rapidly emerging evidence has increasingly supported the view that lncRNAs serve key regulatory and functional roles in mammal cells. HIV-1 replication relies on various cell functions. To date, while the involvement of host protein factors and microRNAs (miRNAs) in the HIV-1 life cycle has been extensively studied, the relationship between lncRNAs and HIV-1 remains uncharacterized. Here, we have profiled 83 disease-related lncRNAs in HIV-1-infected T cells. We found NEAT1 to be one of several lncRNAs whose expression is changed by HIV-1 infection, and we have characterized its role in HIV-1 replication. We In the abstract, added definition of INS OK, or should "cis-acting" be added?report here that the knockdown of NEAT1 enhances virus production through increased nucleus-to-cytoplasm export of Rev-dependent instability element (INS)-containing HIV-1 mRNAs. IMPORTANCE Long protein-noncoding RNAs (lncRNAs) play roles in regulating gene expression and modulating protein activities. There is emerging evidence that lncRNAs are involved in the replication of viruses. To our knowledge, this report is the first to characterize a role contributed by an lncRNA, NEAT1, to HIV-1 replication. NEAT1 is essential for the integrity of the nuclear paraspeckle substructure. Based on our findings from NEAT1 knockdown, we have identified the nuclear paraspeckle body as another important subcellular organelle for HIV-1 replication.
Citations
More filters
Journal ArticleDOI
TL;DR: Nuclear enriched abundant transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, is induced by influenza virus and herpes simplex virus infection as well as by Toll-like receptor3-p38 pathway-triggered poly I:C stimulation, resulting in excess formation of paraspeakles.

536 citations


Cites background from "NEAT1 Long Noncoding RNA and Parasp..."

  • ...Indeed, a recent report observed that NEAT1 modulates HIV-I replication by affecting the nucleus-to-cytoplasm export of Rev-dependent instability element-containing HIV-I mRNAs (Zhang et al., 2013)....

    [...]

Journal ArticleDOI
01 Sep 2019-Cells
TL;DR: The latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma are discussed.
Abstract: The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma.

490 citations


Cites background from "NEAT1 Long Noncoding RNA and Parasp..."

  • ...Both of them are located in nuclear paraspeckles and constitute an important structure of paraspeckles [238]....

    [...]

Journal ArticleDOI
TL;DR: Some state-of-the-art computational models are introduced, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease- related lnc RNAs for experimental validation and discussed the future directions of developing computational models for lncRNA research.
Abstract: LncRNAs have attracted lots of attentions from researchers worldwide in recent decades. With the rapid advances in both experimental technology and computational prediction algorithm, thousands of lncRNA have been identified in eukaryotic organisms ranging from nematodes to humans in the past few years. More and more research evidences have indicated that lncRNAs are involved in almost the whole life cycle of cells through different mechanisms and play important roles in many critical biological processes. Therefore, it is not surprising that the mutations and dysregulations of lncRNAs would contribute to the development of various human complex diseases. In this review, we first made a brief introduction about the functions of lncRNAs, five important lncRNA-related diseases, five critical disease-related lncRNAs and some important publicly available lncRNA-related databases about sequence, expression, function, etc. Nowadays, only a limited number of lncRNAs have been experimentally reported to be related to human diseases. Therefore, analyzing available lncRNA-disease associations and predicting potential human lncRNA-disease associations have become important tasks of bioinformatics, which would benefit human complex diseases mechanism understanding at lncRNA level, disease biomarker detection and disease diagnosis, treatment, prognosis and prevention. Furthermore, we introduced some state-of-the-art computational models, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease-related lncRNAs for experimental validation. We also analyzed the limitations of these models and discussed the future directions of developing computational models for lncRNA research.

439 citations


Cites background from "NEAT1 Long Noncoding RNA and Parasp..."

  • ...Accumulating evidences have further demonstrated that mutations and dysregulations of these lncRNAs are associated with the development and progression of various complex human diseases [21], such as prostate cancer [22, 23], colon cancer [24], lung cancer [25], Alzheimer’s diseases (AD) [26], cardiovascular diseases [27], leukemia [28], diabetes [29], AIDS [30] and neurodegeneration diseases [31]....

    [...]

  • ...Considering the various functions of lncRNAs, it is no surprise to find that the mutations and dysregulations of lncRNAs are closely related to the development and progression of many kinds of human diseases [2, 16, 69, 82, 97–99], such as breast cancer [21, 100], prostate cancer [22, 23], hepatocellular cancer (HCC) [101], colon cancer [24], bladder cancer [34], thyroid cancer [102], lung cancer [25, 103], ovarian cancer [104], AD [26], diabetes [29, 105] and AIDS [30]....

    [...]

Journal ArticleDOI
TL;DR: An unexpectedly dynamic pattern of transcript isoform regulation is found, suggesting a critical regulatory role during HSC differentiation, and a cell cycle/DNA repair signature associated with multipotency in MPP2 cells is found.

409 citations


Cites background from "NEAT1 Long Noncoding RNA and Parasp..."

  • ...AlthoughNeat1 is essential for the integrity of the nuclear substructure, it has also been linked to the immune response after HIV-1 infection (Zhang et al., 2013) and might, therefore, be involved in the maintenance of immune regulatory circuits in MPP3-MPP4....

    [...]

Journal ArticleDOI
TL;DR: Key aspects of lncRNA biology are reviewed, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.
Abstract: The identification of RNAs that are not translated into proteins was an important breakthrough, defining the diversity of molecules involved in eukaryotic regulation of gene expression. These non-coding RNAs can be divided into two main classes according to their length: short non-coding RNAs, such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). The lncRNAs in association with other molecules can coordinate several physiological processes and their dysfunction may impact in several pathologies, including cancer and infectious diseases. They can control the flux of genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability, and post-translational modifications. Long non-coding RNAs present interaction domains for DNA, mRNAs, miRNAs, and proteins, depending on both sequence and secondary structure. The advent of new generation sequencing has provided evidences of putative lncRNAs existence; however, the analysis of transcriptomes for their functional characterization remains a challenge. Here, we review some important aspects of lncRNA biology, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.

403 citations


Cites background from "NEAT1 Long Noncoding RNA and Parasp..."

  • ...Recently, the lncRNAs NEAT1 and MALAT1 were observed colocalizing with nuclear speckles containing the splicing factor SC35 [83]....

    [...]

  • ...A previous study also linked HIV infection with upregulation of lncRNA NEAT1 [162]....

    [...]

  • ...Both miR-101 and miR-217 negatively regulate metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) in carcinoma cells [74], and miR-449a inhibits the expression of nuclear enriched abundant transcript 1 (NEAT1) lncRNA in lung cancer [75]....

    [...]

References
More filters
Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

22,269 citations

Journal ArticleDOI
14 Jun 2007-Nature
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

5,091 citations


"NEAT1 Long Noncoding RNA and Parasp..." refers background in this paper

  • ...It is estimated that more than 70% of the human genome is transcribed into RNA (1, 2), while less than 2% of the total...

    [...]

Journal ArticleDOI
TL;DR: The rapidly advancing field of long ncRNAs is reviewed, describing their conservation, their organization in the genome and their roles in gene regulation, and the medical implications.
Abstract: In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.

4,911 citations


Additional excerpts

  • ...tors in complex regulatory networks (13)....

    [...]

Journal ArticleDOI
08 Aug 2002-Nature
TL;DR: A unique cellular gene, CEM15, is described, whose transient or stable expression in cells that do not normally express Cem15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif.
Abstract: Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo. HIV-1 Vif seems to be required during the late stages of virus production for the suppression of an innate antiviral phenotype that resides in human T lymphocytes. Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif:CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.

2,337 citations

Journal ArticleDOI
08 Jun 2007-Science
TL;DR: Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes and support a highly interleaved organization of the human transcriptome.
Abstract: Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.

2,312 citations


Additional excerpts

  • ...number of protein-noncoding RNAs (ncRNAs) (5)....

    [...]

Related Papers (5)