Abstract:
:Many short-lived mRNAs, including those encoding lymphokines, cytokines, and proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions. These AU domains and, more specifically, AUUUA motifs within them, are widely thought to mediate the extreme instability of the corresponding mRNAs. This is most clearly true for granulocyte monocyte colony stimulating factor (GM-CSF) mRNA whose AUUUA motifs are conserved phylogenetically and whose presence in an otherwise stable beta-globin mRNA results in a 50-fold decrease in accumulated mRNA level. We show that RNA instability conferred by the GM-CSF AU motif requires the mRNA to be actively translated and the AU motif to be within the 3'-untranslated region. By analysis of the sedimentation characteristics, we identify a large (> 20S), divalent cation-independent complex found only on unstable RNAs. Like instability, complex formation (1) is dependent on translation of the RNA, (2) requires intact AUUUA motifs, and (3) is blocked by ribosome translocation across the AU-rich motif. We propose that RNA instability mediated by the AU motif is achieved through translation-dependent assembly of this large mRNA-destabilizing complex.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Savant-Bhonsale S,Cleveland DWdoi
10.1101/gad.6.10.1927subject
Has Abstractpub_date
1992-10-01 00:00:00pages
1927-39issue
10eissn
0890-9369issn
1549-5477journal_volume
6pub_type
杂志文章abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417707
更新日期:2007-05-01 00:00:00
abstract::Mediator was resolved from yeast as a multiprotein complex on the basis of its requirement for transcriptional activation in a fully defined system. Three groups of mediator polypeptides could be distinguished: the products of five SRB genes, identified as suppressors of carboxy-terminal domain (CTD)-truncation mutant...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.1.45
更新日期:1998-01-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.844900
更新日期:2000-11-15 00:00:00
abstract::To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.178962.111
更新日期:2011-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1288
更新日期:1989-09-01 00:00:00
abstract::Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nons...
journal_title:Genes & development
pub_type: 评论
doi:10.1101/gad.329383.119
更新日期:2019-08-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.23.2936
更新日期:1995-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.1.52
更新日期:1990-01-01 00:00:00
abstract::FISH analysis of well-spread chromosomes reveals that homologs are paired in vegetatively growing budding yeast diploid cells, via multiple interstitial interactions, and independent of recA homologs and mating type heterozygosity. Pairing is present during G1 and G2, and in cells arrested at G1 by mating pheromone, b...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.12.1627
更新日期:1999-06-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.7.798
更新日期:1999-04-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.728
更新日期:1991-05-01 00:00:00
abstract::The p53 tumor suppressor is often disrupted in human cancers by the acquisition of missense mutations. We generated mice with a missense mutation at codon 172 that mimics the p53R175H hot spot mutation in human cancer. p53 homozygous mutant mice have unstable mutant p53 in normal cells and stabilize mutant p53 in some...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1662908
更新日期:2008-05-15 00:00:00
abstract::The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations af...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.233395.113
更新日期:2014-01-15 00:00:00
abstract::The yeast HO gene is transcribed transiently during G1 as cells undergo START. START-specific HO activation requires two proteins, SWI4 and SWI6, which act via a motif (CACGA4) repeated up to 10 times within the URS2 region of the HO promoter. We identified a DNA-binding activity containing SWI4 and SWI6 that recogniz...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.11.2000
更新日期:1991-11-01 00:00:00
abstract::Directed cell motility is at the basis of biological phenomena such as development, wound healing, and metastasis. It has been shown that substrate attachments mediate motility by coupling the cell's cytoskeleton with force generation. However, it has been unclear how the persistence of cell directionality is facilita...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.190413.112
更新日期:2012-09-01 00:00:00
abstract::The yeast SAS (Something About Silencing) complex and the histone variant H2A.Z have both previously been linked to an antisilencing function at the subtelomeric regions. SAS is an H4 Lys 16-specific histone acetyltransferase complex. Here we demonstrate that the H4 Lys 16 acetylation by SAS is required for efficient ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1439206
更新日期:2006-09-15 00:00:00
abstract::The gene encoding yeast U6 snRNA that is transcribed by RNA polymerase III (Pol III) contains both a TATA box upstream of the transcription start site and a downstream binding site for the factor TFIIIC. This juxtaposition of elements typical of both Pol II- and Pol III-transcribed genes raises the question of how pol...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.7.832
更新日期:1995-04-01 00:00:00
abstract::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302679.117
更新日期:2017-08-15 00:00:00
abstract::During development of the somatic macronucleus of Tetrahymena thermophila, the rDNA is excised from its germ-line chromosome, rearranged into a palindrome, and amplified to 10(4) copies. We have identified a cis-acting germ-line mutation, rmm11/6, that prevents amplification of the rDNA in all but approximately 1 in 1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.1.84
更新日期:1994-01-01 00:00:00
abstract::Overexpression of the type II transmembrane serine protease matriptase is a highly consistent feature of human epithelial tumors. Here we show that matriptase possesses a strong oncogenic potential when unopposed by its endogenous inhibitor, HAI-1. Modest orthotopic overexpression of matriptase in the skin of transgen...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1300705
更新日期:2005-08-15 00:00:00
abstract::The tobacco mitogen-activated protein kinase (MAPK) cascade, which includes MAPK NRK1/NTF6, positively regulates expansion of the cytokinetic machinery known as the phragmoplast, which is followed by the synthesis of cell plates for completion of cell division. However, molecular events lying between the MAPK and phra...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1408106
更新日期:2006-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.22.3096
更新日期:1997-11-15 00:00:00
abstract::Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281030.116
更新日期:2016-08-01 00:00:00
abstract::Innate immunity against pathogen infection is an evolutionarily conserved process among multicellular organisms. Arabidopsis SNC1 encodes a Resistance protein that combines attributes of multiple mammalian pattern recognition receptors. Utilizing snc1 as an autoimmune model, we identified a discrete protein complex co...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1559607
更新日期:2007-06-15 00:00:00
abstract::Genomic imprinting is an epigenetic phenomenon leading to parentally biased gene expression. Throughout the years, extensive efforts have been made to characterize the epigenetic marks underlying imprinting in animals and plants. As a result, DNA methylation asymmetries between parental genomes emerged as the primary ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.332924.119
更新日期:2020-01-01 00:00:00
abstract::The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.311712.118
更新日期:2018-04-01 00:00:00
abstract::Noncoding RNA regulators have been implicated in almost all imaginable cellular processes. Here we review how regulatory small RNAs such as Spot42, SgrS, GlmY, and GlmZ and a cis-encoded ribozyme in glmS mRNA control sugar metabolism. Besides discussing the physiological implications, we show how the study of these mo...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1717808
更新日期:2008-11-01 00:00:00
abstract::We have used the 100-kD HeLa cell octamer-binding protein OBP100 as a model to study flexible DNA sequence recognition by promoter-binding proteins. OBP100 binds to the conserved octamer motif ATGCAAAT found in numerous promoters and additionally to two degenerate octamer motifs (sites I and II) within the SV40 enhanc...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.11.1400
更新日期:1988-11-01 00:00:00
abstract::Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathway...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.408407
更新日期:2007-03-01 00:00:00
abstract::Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.320069.118
更新日期:2019-01-01 00:00:00