Abstract:
:While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of miRNAs that contain CA and/or UA dinucleotides. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, we report here that cellular TumiD requires UPF1. Results from experiments using AGO2-loaded miRNAs in duplex with target mRNAs indicate that UPF1 can dissociate miRNAs from their mRNA targets, making the miRNAs susceptible to TumiD. miR-seq (deep sequencing of miRNAs) data reveal that the degradation of ∼50% of candidate TumiD targets in T24 human urinary bladder cancer cells is augmented by UPF1. We illustrate the physiological relevance by demonstrating that UPF1-augmented TumiD promotes the invasion of T24 cells in part by degrading anti-invasive miRNAs so as to up-regulate the expression of proinvasive proteins.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Elbarbary RA,Miyoshi K,Hedaya O,Myers JR,Maquat LEdoi
10.1101/gad.303537.117subject
Has Abstractpub_date
2017-07-15 00:00:00pages
1483-1493issue
14eissn
0890-9369issn
1549-5477pii
gad.303537.117journal_volume
31pub_type
杂志文章abstract::In Saccharomyces cerevisiae, the genes encoding the HO endonuclease, G1-specific cyclins CLN1 and CLN2, as well as most proteins involved in DNA synthesis, are periodically transcribed with maximal levels reached in late G1. For HO and the DNA replication genes, cell cycle stage-specific expression has been shown to b...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.4.557
更新日期:1992-04-01 00:00:00
abstract::Integrin receptors for extracellular matrix are critical for cell motility, but the signals that determine when to stop are not known. Analysis of distal tip cell (DTC) migration during gonadogenesis in Caenorhabditis elegans has revealed the importance of transcription factor vab-3/Pax6 in regulating the alpha integr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1534807
更新日期:2007-07-01 00:00:00
abstract::Faithful duplication of the genome relies on the ability to cope with an imperfect template. We investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming. Undamaged origins of replication (oriC) continue to fire at the normal rate and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417607
更新日期:2007-03-15 00:00:00
abstract::The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246256.114
更新日期:2014-10-01 00:00:00
abstract::Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.301887.117
更新日期:2018-01-15 00:00:00
abstract::The E2F transcription factor is required for S phase in Drosophila. While it also triggers expression of replication genes at the G1-S transition, the relevance of this transcription is not clear because many of the induced gene products are sufficiently stable that new expression is not required for S phase. However,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.12.1456
更新日期:1995-06-15 00:00:00
abstract::In many species, a dosage compensation complex (DCC) is targeted to X chromosomes of one sex to equalize levels of X-gene products between males (1X) and females (2X). Here we identify cis-acting regulatory elements that target the Caenorhabditis elegans X chromosome for repression by the DCC. The DCC binds to discret...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1751109
更新日期:2009-03-01 00:00:00
abstract::Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improve...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1333
更新日期:1991-08-01 00:00:00
abstract::Mitotic duration is determined by activation of the anaphase-promoting complex/cyclosome (APC/C) bound to its coactivator, Cdc20. Kinetochores, the microtubule-interacting machines on chromosomes, restrain mitotic exit when not attached to spindle microtubules by generating a Cdc20-containing complex that inhibits the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302067.117
更新日期:2017-06-01 00:00:00
abstract::Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades mRNAs containing premature stop codons (PTCs). In vertebrates, PTCs trigger efficient NMD when located upstream of an exon junction complex (EJC). Degradation of PTC-containing mRNAs requires the endonucleolytic activity of SMG...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.604610
更新日期:2010-11-01 00:00:00
abstract::Staurosporine, a potent inhibitor of protein kinase C, arrests fission yeast cell elongation specifically at a stage immediately after cell division. We isolated two genes, which, when carried on multicopy plasmids, confer drug resistance in fission yeast. One, spk1+, encodes a protein kinase highly similar (54% ident...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.1.60
更新日期:1991-01-01 00:00:00
abstract::The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional module. RNAi depletion and overexpression experiments revealed a genetic circuit that controls the balance of transcription from two core promoter motifs, the TATA box and the downstream core promoter element (DPE). In this ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1681808
更新日期:2008-09-01 00:00:00
abstract::The recombinational enhancer of the Hin inversion system in Salmonella stimulates recombination in vitro 150-fold in the presence of the Escherichia coli host factor Fis. To gain an understanding of the roles of the enhancer and Fis in stimulating the Hin-mediated inversion reaction, we have used nuclease and chemical...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.8.762
更新日期:1987-10-01 00:00:00
abstract::The ECS (Elongin B/C-Cul2/Cul5-SOCS-box protein) complex is a member of a family of ubiquitin ligases that share a Cullin-Rbx module. SOCS-box proteins recruit substrates to the ECS complex and are linked to Cullin-Rbx via Elongin B/C. VHL has been implicated as a SOCS-box protein, but lacks a C-terminal sequence (dow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1252404
更新日期:2004-12-15 00:00:00
abstract::Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose depriv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1985910
更新日期:2010-12-15 00:00:00
abstract::The essential splicing factor human UAP56 (hUAP56) is a DExD/H-box protein known to promote prespliceosome assembly. Here, using a series of hUAP56 mutants that are defective for ATP-binding, ATP hydrolysis, or dsRNA unwindase/helicase activity, we assess the relative contributions of these biochemical functions to pr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1657308
更新日期:2008-07-01 00:00:00
abstract::Morphogen gradients of secreted molecules play critical roles in the establishment of the spatial pattern of gene expression. During midgut development in Drosophila, secreted molecules of Decapentaplegic (Dpp) and Wingless (Wg) establish unique transcriptional regulation within target cells to specify the resultant c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.17.2724
更新日期:1998-09-01 00:00:00
abstract::MicF, one of the first chromosomally encoded regulatory small RNAs (sRNAs) to be discovered, was found to modulate the expression of OmpF, an abundant outer membrane protein. Several recent papers have now shown that this is not an isolated case. At least five other sRNAs also regulate the synthesis of outer membrane ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1457506
更新日期:2006-09-01 00:00:00
abstract::TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in exci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.194829.112
更新日期:2012-08-01 00:00:00
abstract::Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins. Among the many PcG proteins known in Drosophila, Pho is the only sequence-specific DNA-binding protein. To gain insight into the function of Pho,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377406
更新日期:2006-05-01 00:00:00
abstract::S-phase cyclin-dependent kinase Cdc28-Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7-Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is also essential for initiation of meiotic recombination because it phosphorylates Ser30 of Mer2, a meiosis-specific double-s...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1626408
更新日期:2008-02-01 00:00:00
abstract::The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA sy...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.23.3639
更新日期:1998-12-01 00:00:00
abstract::Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.6.770
更新日期:1989-06-01 00:00:00
abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.6.740
更新日期:1996-03-15 00:00:00
abstract::We hypothesized that basic helix-loop-helix (bHLH) MIST1 (BHLHA15) is a "scaling factor" that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PC...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.285684.116
更新日期:2017-01-15 00:00:00
abstract::SNF2 chromatin-remodeling ATPases play an important role in ensuring proper development in higher eukaryotes by controlling accessibility of cis-regulatory DNA regions to transcription factors and to the transcriptional machinery. However, the biological targets controlled by these ATPases are largely unknown. Using g...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1276305
更新日期:2005-04-15 00:00:00
abstract::Eukaryotic morphogenesis is seeded with the establishment and subsequent amplification of polarity cues at key times during the cell cycle, often using (cyclic) nucleotide signals. We discovered that flagellum de- and repolarization in the model prokaryote Caulobacter crescentus is precisely orchestrated through at le...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.222679.113
更新日期:2013-09-15 00:00:00
abstract::The oncoprotein MDM2 binds to the activation domain of the tumor suppressor p53 and inhibits its ability to stimulate transcription. This same region of p53 is able to bind several basal transcription factors that appear to be important for the transactivation function of p53. It has therefore been suggested that MDM2...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.15.1974
更新日期:1997-08-01 00:00:00
abstract::A conditional allele of type 1 protein phosphatase (glc7-129) in Saccharomyces cerevisiae causes first cycle arrest in G2/M, characterized by cells with a short spindle and high H1 kinase activity. Point-of-execution experiments indicate Glc7p function is required in G2/M just before anaphase for the completion of mit...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.5.517
更新日期:1999-03-01 00:00:00
abstract::The formins constitute a set of protein isoforms encoded by the alternatively spliced transcripts arising from the limb deformity (ld) locus of the mouse. Mutations in this locus disrupt formation of the anteroposterior axis of the embryonic limb. Although ld transcripts are widely expressed during embryogenesis, we h...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.1.29
更新日期:1992-01-01 00:00:00