Abstract:
:Influenza virus unspliced NS1 mRNA, like retroviral pre-mRNAs, is efficiently exported from the nucleus and translated in the cytoplasm of infected cells. With human immunodeficiency virus (HIV), the transport of viral pre-mRNAs is facilitated by the viral Rev protein. We tested the possibility that the influenza virus NS1 protein, a nuclear protein that is encoded by unspliced NS1 mRNA, has the same function as the HIV Rev protein. Surprisingly, using transient transfection assays, we found that rather than facilitating the nucleocytoplasmic transport of unspliced NS1 mRNA, the NS1 protein inhibited the transport of NS2 mRNA, the spliced mRNA generated from NS1 mRNA. The efficient transport of NS2 mRNA from the nucleus to the cytoplasm occurred only when the synthesis of the NS1 protein was abrogated by amber mutations. The NS1 protein down-regulated the export of NS2 mRNA whether or not it was generated by splicing, indicating that the NS1 protein acted directly on transport. Actinomycin D chase experiments verified that the NS1 protein acted on the transport and not on the differential stability of NS2 mRNA in the nucleus as compared to the cytoplasm. In addition, the NS1 protein inhibited the transport of NS1 mRNA itself, which contains all of the sequences in NS2 mRNA, particularly when NS1 mRNA was released from the splicing machinery by mutating its 3'-splice site. Our results indicate that the NS1 protein-mediated inhibition of transport requires sequences in NS2 mRNA. The transport of the viral PB1 protein, nucleocapsid protein, hemagglutinin, membrane protein, and M2 mRNAs was not affected by the NS1 protein. When the NS2 mRNA sequence was covalently attached to the PB1 mRNA, the transport of the chimeric mRNA was inhibited by the NS1 protein. Our results identify a novel function of the influenza virus NS1 protein and demonstrate that post-transcriptional control of gene expression can also occur at the level of the nucleocytoplasmic transport of a mature, spliced mRNA.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Alonso-Caplen FV,Nemeroff ME,Qiu Y,Krug RMdoi
10.1101/gad.6.2.255subject
Has Abstractpub_date
1992-02-01 00:00:00pages
255-67issue
2eissn
0890-9369issn
1549-5477journal_volume
6pub_type
杂志文章abstract::Transcription of the cell-cycle-regulated human histone genes increases approximately fivefold during S phase. One step toward the elucidation of the biochemical mechanisms that govern cell-cycle-regulated expression of these genes is to purify and characterize the transcription factors that regulate these promoters. ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1700
更新日期:1988-12-01 00:00:00
abstract::The Ultrabithorax (Ubx) gene of Drosophila melanogaster encodes a family of UBX proteins that are thought to specify the developmental fates of segments in the posterior thorax and anterior abdomen by controlling the expression of a set of target genes. UBX proteins bind DNA in vitro, and they activate or repress diff...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.6.1044
更新日期:1990-06-01 00:00:00
abstract::The abundance of retinoic acid (RA) is determined by the balance between its synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In particular, the dynamic expression of three CYP26 genes controls the regional level of RA within the body. Pregastrulation mouse embryos express CYP26 but not R...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1776209
更新日期:2009-07-15 00:00:00
abstract::Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.391106
更新日期:2006-11-01 00:00:00
abstract::Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.307132.117
更新日期:2018-03-01 00:00:00
abstract::The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1170904
更新日期:2004-03-15 00:00:00
abstract::The myc family of cellular oncogenes encodes three highly related nuclear phosphoproteins (c-Myc, N-Myc, and L-Myc) that are believed to function as sequence-specific transcription factors capable of regulating genes important in cellular growth and differentiation. Current evidence indicates that Myc family proteins ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.8.1480
更新日期:1992-08-01 00:00:00
abstract::Cellular senescence is a potent tumor suppressor mechanism but also contributes to aging and aging-related diseases. Senescence is characterized by a stable cell cycle arrest and a complex proinflammatory secretome, termed the senescence-associated secretory phenotype (SASP). We recently discovered that cytoplasmic ch...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.331272.119
更新日期:2020-03-01 00:00:00
abstract::One of the central requirements for eukaryotic chromosome stability is the maintenance of the simple sequence tracts at telomeres. In this study, we use genetic and physical assays to reveal the nature of a novel mechanism by which telomere length is controlled. This mechanism, telomeric rapid deletion (TRD), is capab...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.11.1310
更新日期:1996-06-01 00:00:00
abstract::The fission yeast telomerase RNA (TER1) precursor harbors an intron immediately downstream from its mature 3' end. Unlike most introns, which are removed from precursor RNAs by the spliceosome in two sequential but tightly coupled transesterification reactions, TER1 only undergoes the first cleavage reaction during te...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.212738.112
更新日期:2013-03-15 00:00:00
abstract::Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.9.1560
更新日期:1990-09-01 00:00:00
abstract::Chromatin reorganization is essential for transcriptional control by sequence-specific transcription factors. However, the molecular link between transcriptional control and chromatin reconfiguration remains unclear. By colocalization of the nuclear ecdysone receptor (EcR) on the ecdysone-induced puff in the salivary ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1857410
更新日期:2010-01-15 00:00:00
abstract::During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains of dorsal and ventral fate, then further patterned to generate somitic mesoderm by signals from the gastrula organizer. Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to di...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.21.2805
更新日期:1996-11-01 00:00:00
abstract::Ubiquitin-mediated proteolysis controls the abundance of many cell cycle regulatory proteins. Recent work in Saccharomyces cerevisiae suggests that a complex consisting of Cdc53, Skp1, and a third component known as an F-box protein (termed SCF) in combination with Cdc34 specifically targets regulatory proteins for de...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.16.2587
更新日期:1998-08-15 00:00:00
abstract::Establishment of the steroid-producing Leydig cell lineage is an event downstream of Sry that is critical for masculinization of mammalian embryos. Neither the origin of fetal Leydig cell precursors nor the signaling pathway that specifies the Leydig cell lineage is known. Based on the sex-specific expression patterns...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.981202
更新日期:2002-06-01 00:00:00
abstract::Bone morphogenic proteins 2 and 4 (BMP2 and BMP4) inhibit proliferation and induce differentiation of cerebellar granule neuron progenitors (GNPs) and primary GNP-like medulloblastoma (MB) cells. This occurs through rapid proteasome-mediated degradation of Math1 (Atoh1), a transcription factor expressed in proliferati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1636408
更新日期:2008-03-15 00:00:00
abstract::In meiosis I, homologous chromosomes pair and then attach to the spindle so that the homologs can be pulled apart at anaphase I. The segregation of homologs before pairing would be catastrophic. We describe two mechanisms that prevent this. First, in early meiosis, Ipl1, the budding yeast homolog of the mammalian Auro...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.227454.113
更新日期:2013-10-01 00:00:00
abstract::High-fidelity chromosome transmission is fundamental in controlling the quality of the cell division cycle. The spindle pole-to-pole distance remains constant from metaphase to anaphase A. We show that fission yeast sister centromere-connecting proteins, Mis6 and Mis12, are required for correct spindle morphogenesis, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.13.1664
更新日期:1999-07-01 00:00:00
abstract::Chromosomal processes related to formation and function of meiotic chiasmata have been analyzed in Sordaria macrospora. Double-strand breaks (DSBs), programmed or gamma-rays-induced, are found to promote four major events beyond recombination and accompanying synaptonemal complex formation: (1) juxtaposition of homolo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.275203
更新日期:2003-11-01 00:00:00
abstract::The connection between RNA and protein export from the nucleus was examined in the budding yeast Saccharomyces cerevisiae. NPL3 encodes an RNA-binding protein that shuttles in and out of the nucleus. Export of poly(A)+ RNA has been shown previously to be blocked in np13-1 mutants. To understand the role of Np13p in RN...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.10.1233
更新日期:1996-05-15 00:00:00
abstract::A prominent feature of cell differentiation is the initiation and maintenance of an irreversible cell cycle arrest with the complex involvement of the retinoblastoma (RB) family (RB, p130, p107). We have isolated the HBP1 transcriptional repressor as a potential target of the RB family in differentiated cells. By homo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.3.383
更新日期:1997-02-01 00:00:00
abstract::The X-inactive-specific transcript (Xist) locus is a cis-acting switch that regulates X chromosome inactivation in mammals. Over recent years an important goal has been to understand how Xist is regulated at the initiation of X inactivation. Here we report the analysis of a series of targeted mutations at the 5' end o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271203
更新日期:2003-09-01 00:00:00
abstract::Two retrovirus promoter trap vectors (U3His and U3Neo) have been used to disrupt genes expressed in totipotent murine embryonal stem (ES) cells. Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.919
更新日期:1992-06-01 00:00:00
abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.285460.116
更新日期:2016-07-01 00:00:00
abstract::Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for api...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.20.3156
更新日期:1998-10-15 00:00:00
abstract::Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naïve mo...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
doi:10.1101/gad.302364.117
更新日期:2017-05-15 00:00:00
abstract::Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.297135.117
更新日期:2017-05-15 00:00:00
abstract::Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encod...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.288555.116
更新日期:2017-01-15 00:00:00
abstract::The Caenorhabditis elegans caudal homolog, pal-1, is required for neurogenesis in the male tail. We show that expression of pal-1 in the postembryonic neuroblast cell V6 can be initiated by two alternate pathways. One pathway, acting in wild type, requires a regulatory element in the fifth pal-1 intron. The other path...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.814700
更新日期:2000-09-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arose very early during eukaryotic evolution, and its ancestral role may have been in the response to starvation. Recent work shows that the kinase is activated by increases not only in AMP, but also in ADP....
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.17420111
更新日期:2011-09-15 00:00:00