Abstract:
:At least half of all human pre-mRNAs are subject to alternative 3' processing that may modulate both the coding capacity of the message and the array of post-transcriptional regulatory elements embedded within the 3' UTR. Vertebrate poly(A) site selection appears to rely primarily on the binding of CPSF to an A(A/U)UAAA hexamer upstream of the cleavage site and CstF to a downstream GU-rich element. At least one-quarter of all human poly(A) sites, however, lack the A(A/U)UAAA motif. We report that sequence-specific RNA binding of the human 3' processing factor CFI(m) can function as a primary determinant of poly(A) site recognition in the absence of the A(A/U)UAAA motif. CFI(m) is sufficient to direct sequence-specific, A(A/U)UAAA-independent poly(A) addition in vitro through the recruitment of the CPSF subunit hFip1 and poly(A) polymerase to the RNA substrate. ChIP analysis indicates that CFI(m) is recruited to the transcription unit, along with CPSF and CstF, during the initial stages of transcription, supporting a direct role for CFI(m) in poly(A) site recognition. The recognition of three distinct sequence elements by CFI(m), CPSF, and CstF suggests that vertebrate poly(A) site definition is mechanistically more similar to that of yeast and plants than anticipated.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Venkataraman K,Brown KM,Gilmartin GMdoi
10.1101/gad.1298605subject
Has Abstractpub_date
2005-06-01 00:00:00pages
1315-27issue
11eissn
0890-9369issn
1549-5477pii
19/11/1315journal_volume
19pub_type
杂志文章abstract::The Hedgehog (Hh) family of secreted proteins controls many aspects of animal development. In Drosophila, Hh transduces its signal via Cubitus interruptus (Ci), a transcription factor present in two forms: a full-length activator and a carboxy-terminally truncated repressor that is derived from the full-length form by...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.21.2828
更新日期:1999-11-01 00:00:00
abstract::DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3331
更新日期:1998-11-01 00:00:00
abstract::NF-kappa B is an inducible transcription factor comprised of a 50-kD (p50) and a 65-kD (p65) subunit. Induction of NF-kappa B activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, I kappa B, followed by translocation of the active transcriptio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.1899
更新日期:1992-10-01 00:00:00
abstract::The mechanisms that determine the relative positions of floral organs, and thereby their numbers, is a poorly understood aspect of flower development. We isolated a petunia mutant, floozy (fzy), in which the formation of floral organ primordia in the outermost three floral whorls and one of the two bracts at the base ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.219502
更新日期:2002-03-15 00:00:00
abstract::In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 (ATR) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subuni...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256958.114
更新日期:2015-04-01 00:00:00
abstract::Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has rem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.246538.114
更新日期:2014-11-15 00:00:00
abstract::Mesoderm induction assays in Xenopus have implicated growth factors such as activin, Vg1, Xwnt-8, and noggin as important in directing the formation of dorsal mesoderm (Spemann's organizer). Because these growth factors are structurally very different, they presumably act through distinct cell surface receptors that i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3038
更新日期:1995-12-15 00:00:00
abstract::Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.6.1072
更新日期:1993-06-01 00:00:00
abstract::The presence of a single EGF receptor in Drosophila is contrasted by multiple ligands activating it. This work explores the role of two ligands, Spitz and Vein, in the embryonic ventral ectoderm. Spitz is a potent ligand, whereas Vein is an intrinsically weak activating ligand. We show that secreted Spitz emanating fr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.2.158
更新日期:1999-01-15 00:00:00
abstract::The Dorsal morphogen is a transcription factor that activates some genes and represses others to establish multiple domains of gene expression along the dorsal/ventral axis of the early Drosophila embryo. Repression by Dorsal appears to require accessory proteins that bind to corepression elements in Dorsal-dependent ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3177
更新日期:1995-12-15 00:00:00
abstract::In budding yeast, a switch between the mutually exclusive pathways of cell cycle progression and conjugation is controlled at Start in late G1 phase. Mating pheromones promote conjugation by arresting cells in G1 phase before Start. Pheromone-induced cell cycle arrest requires a functional FAR1 gene. We have found tha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.5.833
更新日期:1993-05-01 00:00:00
abstract::The third-chromosome mutation Killer of prune (K-pn) causes no phenotype by itself, but causes lethality in individuals homozygous for the nonlethal X-chromosome mutation prune (pn). We have recovered 12 gamma-ray-induced revertants of Killer of prune. All of the revertants fail to complement a recessive cell lethal m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.10.1333
更新日期:1988-10-01 00:00:00
abstract::The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc nul...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2248
更新日期:1992-12-01 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::Chemical mutagenesis in the mouse is a powerful approach for phenotype-driven genetics, but questions remain about the efficiency with which new mutations ascertained by their phenotype can be localized and identified, and that knowledge applied to a specific biological problem. During a global screen for dominant phe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1023703
更新日期:2003-01-15 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 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
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::Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily conserved histone H3 variant, which directs kinetochore assembly and hence centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity-selected solubilized fission yeast CENP-ACnp1 chromatin. All ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.332536.119
更新日期:2020-02-01 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::Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating heterochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heteroch...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.272237.115
更新日期:2016-03-01 00:00:00
abstract::Ectopic repression of retinoic acid (RA) receptor target genes by PML/RARA and PLZF/RARA fusion proteins through aberrant recruitment of nuclear corepressor complexes drives cellular transformation and acute promyelocytic leukemia (APL) development. In the case of PML/RARA, this repression can be reversed through trea...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.512009
更新日期:2009-05-15 00:00:00
abstract::The incorporation of histone H1 into chromatin during embryogenesis directs the specific repression of the Xenopus oocyte 5S rRNA genes. An increase in histone H1 content specifically restricts TFIIIA-activated transcription, and a decrease in histone H1 within chromatin facilitates the activation of the oocyte 5S rRN...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.10.1147
更新日期:1994-05-15 00:00:00
abstract::YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. Aberrant hyperactivation of YAP/TAZ causes tissue overgrowth and tumorigenesis, whereas their inactivatio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.262816.115
更新日期:2015-06-15 00:00:00
abstract::As in many polarized cells, spindle alignment in yeast is essential and cell cycle regulated. A key step that governs spindle alignment is the selective binding of the Kar9 protein to only one of the two spindle pole bodies (SPBs). It has been suggested that cyclin-dependent kinase Cdc28, in complex with cyclin Clb4, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.298704
更新日期:2004-07-15 00:00:00
abstract::The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.24.3105
更新日期:1996-12-15 00:00:00
abstract::Commitment to mitosis is regulated by a protein kinase complex called MPF. MPF is inhibited by Wee1-related kinases and activated by Cdc25 phosphatase. MPF activation further boosts Cdc25 and represses Wee1. This feedback control probably involves polo kinase. A dominant cut12.s11 mutation in the Schizosaccharomyces p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256003
更新日期:2003-06-15 00:00:00
abstract::We showed previously that the MAP kinase ERK2 is essential for aggregation. erk2 null cells lack cAMP stimulation of adenylyl cyclase and thus cannot relay the cAMP chemotactic signal, although the cells chemotax to cAMP (Segall et al. 1995). In this paper we have examined the role of ERK2 in controlling developmental...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.1.118
更新日期:1996-01-01 00:00:00
abstract::Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.943001
更新日期:2001-12-15 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