Regulation of c-myc mRNA decay by translational pausing in a coding region instability determinant.

Abstract:

:A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage. However, it was unclear why a CRD-BP is required to protect a well-translated mRNA whose coding region is covered with ribosomes. We hypothesized that translational pausing in the CRD generates a ribosome-deficient region downstream of the pause site, and this region is exposed to endonuclease attack unless it is shielded by the CRD-BP. Transfection and cell-free translation experiments reported here support this hypothesis. Ribosome pausing occurs within the c-myc CRD in tRNA-depleted reticulocyte translation reactions. The pause sites map to a rare arginine (CGA) codon and to an adjacent threonine (ACA) codon. Changing these codons to more common codons increases translational efficiency in vitro and increases mRNA abundance in transfected cells. These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs. Additional mapping experiments suggest that the CRD is bipartite, with several upstream translation pause sites and a downstream endonuclease cleavage site.

journal_name

Mol Cell Biol

authors

Lemm I,Ross J

doi

10.1128/mcb.22.12.3959-3969.2002

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

3959-69

issue

12

eissn

0270-7306

issn

1098-5549

journal_volume

22

pub_type

杂志文章
  • MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C.

    abstract::The PKC1 gene of Saccharomyces cerevisiae encodes a homolog of mammalian protein kinase C that is required for normal growth and division of yeast cells. We report here the isolation of the yeast MKK1 and MKK2 (for mitogen-activated protein [MAP] kinase-kinase) genes which, when overexpressed, suppress the cell lysis ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.5.3076

    authors: Irie K,Takase M,Lee KS,Levin DE,Araki H,Matsumoto K,Oshima Y

    更新日期:1993-05-01 00:00:00

  • The nuclear pore complex and the DEAD box protein Rat8p/Dbp5p have nonessential features which appear to facilitate mRNA export following heat shock.

    abstract::Nuclear pore complexes (NPCs) play an essential role in RNA export. Nucleoporins required for mRNA export in Saccharomyces cerevisiae are found in the Nup84p and Nup82p subcomplexes of the NPC. The Nup82p subcomplex contains Nup82p, Rat7p/Nup159p, Nsp1p, Gle1p/Rss1p, and Rip1p/Nup42p and is found only on the cytoplasm...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.11.4869-4879.2004

    authors: Rollenhagen C,Hodge CA,Cole CN

    更新日期:2004-06-01 00:00:00

  • The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development.

    abstract::Hox11 is a homeobox gene essential for spleen formation in mice, since atrophy of the anlage of a developing spleen occurs in early embryonic development in Hox11 null mice. HOX11 is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations. Since the protein has a homeodomain and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.12.7030

    authors: Greene WK,Bahn S,Masson N,Rabbitts TH

    更新日期:1998-12-01 00:00:00

  • Coordination of RNA Polymerase II Pausing and 3' End Processing Factor Recruitment with Alternative Polyadenylation.

    abstract::Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00898-15

    authors: Fusby B,Kim S,Erickson B,Kim H,Peterson ML,Bentley DL

    更新日期:2015-11-02 00:00:00

  • Tissue localization of Drosophila melanogaster ras transcripts during development.

    abstract::Three ras homologs have been identified in Drosophila melanogaster. Here we describe the tissue distribution of their transcripts as analyzed by in situ hybridization. The RNAs of the three genes show a similar distribution at every developmental stage examined. In embryos, the transcripts are uniformly distributed. I...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.6.2241

    authors: Segal D,Shilo BZ

    更新日期:1986-06-01 00:00:00

  • The N Termini of TAR DNA-Binding Protein 43 (TDP43) C-Terminal Fragments Influence Degradation, Aggregation Propensity, and Morphology.

    abstract::Fragments of the TAR DNA-binding protein 43 (TDP43) are major components of intracellular aggregates associated with amyotrophic lateral sclerosis and frontotemporal dementia. A variety of C-terminal fragments (CTFs) exist, with distinct N termini; however, little is known regarding their differences in metabolism and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00243-18

    authors: Kasu YAT,Alemu S,Lamari A,Loew N,Brower CS

    更新日期:2018-09-14 00:00:00

  • Mitochondrial import and processing of mutant human ornithine transcarbamylase precursors in cultured cells.

    abstract::We have investigated mitochondrial import and processing of the precursor for human ornithine transcarbamylase (OTC; carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3) in HeLa cells stably transformed with cDNA sequences encoding OTC precursors carrying mutations in their leader peptides. The mutant prec...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.12.5150

    authors: Isaya G,Fenton WA,Hendrick JP,Furtak K,Kalousek F,Rosenberg LE

    更新日期:1988-12-01 00:00:00

  • E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro-T cells that cause acute T-lymphoid or myeloid leukemias in mice.

    abstract::Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cult...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.3.1256-1269.2004

    authors: Sykes DB,Kamps MP

    更新日期:2004-02-01 00:00:00

  • Transcription alters chromosomal locations of cohesin in Saccharomyces cerevisiae.

    abstract::In eukaryotic cells, cohesion between sister chromatids allows chromosomes to biorient on the metaphase plate and holds them together until they separate into daughter cells during mitosis. Cohesion is mediated by the cohesin protein complex. Although the association of this complex with particular regions of the geno...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01007-07

    authors: Bausch C,Noone S,Henry JM,Gaudenz K,Sanderson B,Seidel C,Gerton JL

    更新日期:2007-12-01 00:00:00

  • The capable ABL: what is its biological function?

    abstract::The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL als...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审

    doi:10.1128/MCB.01454-13

    authors: Wang JY

    更新日期:2014-04-01 00:00:00

  • Role of poly(A) polymerase in the cleavage and polyadenylation of mRNA precursor.

    abstract::To determine the role of poly(A) polymerase in 3'-end processing of mRNA, the effect of purified poly(A) polymerase antibodies on endonucleolytic cleavage and polyadenylation was studied in HeLa nuclear extracts, using adenovirus L3 pre-mRNA as the substrate. Both Mg2+- and Mn2+-dependent reactions catalyzing addition...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.4.1435

    authors: Terns MP,Jacob ST

    更新日期:1989-04-01 00:00:00

  • Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways.

    abstract::Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the eff...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.8.4117

    authors: Klippel A,Reinhard C,Kavanaugh WM,Apell G,Escobedo MA,Williams LT

    更新日期:1996-08-01 00:00:00

  • Fal1p is an essential DEAD-box protein involved in 40S-ribosomal-subunit biogenesis in Saccharomyces cerevisiae.

    abstract::A previously uncharacterized Saccharomyces cerevisiae gene, FAL1, was found by sequence comparison as a homolog of the eukaryotic translation initiation factor 4A (eIF4A). Fal1p has 55% identity and 73% similarity on the amino acid level to yeast eIF4A, the prototype of ATP-dependent RNA helicases of the DEAD-box prot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.7283

    authors: Kressler D,de la Cruz J,Rojo M,Linder P

    更新日期:1997-12-01 00:00:00

  • LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein.

    abstract::The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.1.644

    authors: Taniguchi Y,Furukawa T,Tun T,Han H,Honjo T

    更新日期:1998-01-01 00:00:00

  • Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated.

    abstract::HO endonuclease-induced double-strand breaks in Saccharomyces cerevisiae can undergo recombination by two distinct and competing pathways. In a plasmid containing a direct repeat, in which one repeat is interrupted by an HO endonuclease cut site, gap repair yields gene conversions while single-strand annealing produce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.3.1292

    authors: Fishman-Lobell J,Rudin N,Haber JE

    更新日期:1992-03-01 00:00:00

  • LZTS2 is a novel beta-catenin-interacting protein and regulates the nuclear export of beta-catenin.

    abstract::Beta-catenin plays multiple roles in cell-cell adhesion and Wnt signal transduction. Through the Wnt signal, the cellular level of beta-catenin is constitutively regulated by the multicomponent destruction complex containing glycogen synthase kinase 3beta, axin, and adenomatous polyposis coli. Here, we present multipl...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01031-06

    authors: Thyssen G,Li TH,Lehmann L,Zhuo M,Sharma M,Sun Z

    更新日期:2006-12-01 00:00:00

  • The Mauriceville retroplasmid reverse transcriptase initiates cDNA synthesis de novo at the 3' end of tRNAs.

    abstract::The Mauriceville retroplasmid of Neurospora mitochondria encodes a novel reverse transcriptase that initiates cDNA synthesis de novo (i.e., without a primer) at the 3' CCA of the plasmid transcript's 3' tRNA-like structure (H. Wang and A. M. Lambowitz, Cell 75:1071-1081, 1993). Here, we show that the plasmid reverse t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.8.4526

    authors: Chiang CC,Lambowitz AM

    更新日期:1997-08-01 00:00:00

  • CAPNS1 regulates USP1 stability and maintenance of genome integrity.

    abstract::Calpains regulate a wide spectrum of biological functions, including migration, adhesion, apoptosis, secretion, and autophagy, through the modulating cleavage of specific substrates. Ubiquitous microcalpain (μ-calpain) and millicalpain (m-calpain) are heterodimers composed of catalytic subunits encoded, respectively, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01406-12

    authors: Cataldo F,Peche LY,Klaric E,Brancolini C,Myers MP,Demarchi F,Schneider C

    更新日期:2013-06-01 00:00:00

  • Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10.

    abstract::Dominant mutations in the early growth response 2 (Egr2/Krox20) transactivator, a critical regulator of peripheral myelin development, have been associated with peripheral myelinopathies. These dominant mutants interfere with the expression of genes required for myelination by Schwann cells, including that for the mos...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01689-06

    authors: LeBlanc SE,Ward RM,Svaren J

    更新日期:2007-05-01 00:00:00

  • Dax1 binds to Oct3/4 and inhibits its transcriptional activity in embryonic stem cells.

    abstract::Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor Oct3/4 is an indispensable factor in the self-renewal of ES cells. In this study, we searched for a protein that would interact with Oct3/4 in ES cells and identified an orphan nuclear hormone receptor...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01863-08

    authors: Sun C,Nakatake Y,Akagi T,Ura H,Matsuda T,Nishiyama A,Koide H,Ko MS,Niwa H,Yokota T

    更新日期:2009-08-01 00:00:00

  • The low-abundance U11 and U12 small nuclear ribonucleoproteins (snRNPs) interact to form a two-snRNP complex.

    abstract::A novel small nuclear ribonucleoprotein (snRNP) complex containing both U11 and U12 RNAs has been identified in HeLa cell extracts. This U11/U12 snRNP complex can be visualized on glycerol gradients, on native polyacrylamide gels, and by selection with antisense 2'-O-methyl oligoribonucleotides. RNase H-mediated degra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.3.1276

    authors: Wassarman KM,Steitz JA

    更新日期:1992-03-01 00:00:00

  • Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation.

    abstract::Epidermal growth factor (EGF) induces tyrosine phosphorylation of the Shc adapter protein, which plays an important role in EGF-stimulated mitogenesis. Shc stimulates Ras/mitogen-activated protein kinase (MAPK) through forming a complex with Grb2 at the phosphorylated tyrosine (Y) residue 317. In this study, we identi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.4.1824

    authors: Gotoh N,Toyoda M,Shibuya M

    更新日期:1997-04-01 00:00:00

  • The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts.

    abstract::A set of genes is rapidly inducible when quiescent fibroblasts are stimulated by growth factors or by the activation of temperature-sensitive retroviral protein-tyrosine kinases. Most of these so-called immediate-early genes were cloned by differential cDNA hybridization. DNA sequence analysis identified many of them ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.7.3682

    authors: Jähner D,Hunter T

    更新日期:1991-07-01 00:00:00

  • Regulation of cell size by glucose is exerted via repression of the CLN1 promoter.

    abstract::Yeast cells are keenly sensitive to the availability and quality of nutrients. Addition of glucose to cells growing on a poorer carbon source elicits a cell cycle delay during G1 phase and a concomitant increase in the cell size. The signal is transduced through the RAS-cyclic AMP pathway. Using synchronized populatio...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.5.2492

    authors: Flick K,Chapman-Shimshoni D,Stuart D,Guaderrama M,Wittenberg C

    更新日期:1998-05-01 00:00:00

  • An octamer motif contributes to the expression of the retinoic acid-regulated zinc finger gene Rex-1 (Zfp-42) in F9 teratocarcinoma cells.

    abstract::The message for the zinc finger gene Rex-1 (Zfp-42) is expressed in undifferentiated murine F9 teratocarcinoma cells and embryonic stem cells. Expression of Rex-1 is reduced at the transcriptional level when F9 cells are induced by the addition of retinoic acid (RA) to differentiate. We have isolated genomic DNA for t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.5.2919

    authors: Hosler BA,Rogers MB,Kozak CA,Gudas LJ

    更新日期:1993-05-01 00:00:00

  • Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

    abstract::Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.4.1846

    authors: Riccio A,Pedone PV,Lund LR,Olesen T,Olsen HS,Andreasen PA

    更新日期:1992-04-01 00:00:00

  • IκB kinase 2 regulates TPL-2 activation of extracellular signal-regulated kinases 1 and 2 by direct phosphorylation of TPL-2 serine 400.

    abstract::Tumor progression locus 2 (TPL-2) functions as a MEK-1/2 kinase, which is essential for Toll-like receptor 4 (TLR4) activation of extracellular signal-regulated kinase 1 and 2 (ERK-1/2) mitogen-activated protein (MAP) kinases in lipopolysaccharide (LPS)-stimulated macrophages and for inducing the production of the pro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01065-12

    authors: Roget K,Ben-Addi A,Mambole-Dema A,Gantke T,Yang HT,Janzen J,Morrice N,Abbott D,Ley SC

    更新日期:2012-11-01 00:00:00

  • Yeast Dun1 kinase regulates ribonucleotide reductase inhibitor Sml1 in response to iron deficiency.

    abstract::Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox-active cofactor in many biological processes, including DNA replication and repair. Eukaryotic ribonucleotide reductases (RNRs) are Fe-dependent enzymes that catalyze deoxyribonucleoside diphosphate (dNDP) synthesis. We ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00472-14

    authors: Sanvisens N,Romero AM,An X,Zhang C,de Llanos R,Martínez-Pastor MT,Bañó MC,Huang M,Puig S

    更新日期:2014-09-01 00:00:00

  • Differential recognition of response elements determines target gene specificity for p53 and p63.

    abstract::p63 is a member of the p53 tumor suppressor gene family, which regulates downstream target gene expression by binding to sequence-specific response elements similar to those of p53. By using oligonucleotide expression microarray analysis and analyzing the promoters of p63-induced genes, we have identified novel p63-sp...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.14.6077-6089.2005

    authors: Osada M,Park HL,Nagakawa Y,Yamashita K,Fomenkov A,Kim MS,Wu G,Nomoto S,Trink B,Sidransky D

    更新日期:2005-07-01 00:00:00

  • Mutations in the yeast KEX2 gene cause a Vma(-)-like phenotype: a possible role for the Kex2 endoprotease in vacuolar acidification.

    abstract::Mutants of Saccharomyces cerevisiae that lack vacuolar proton-translocating ATPase (V-ATPase) activity show a well-defined set of Vma- (stands for vacuolar membrane ATPase activity) phenotypes that include pH-conditional growth, increased calcium sensitivity, and the inability to grow on nonfermentable carbon sources....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.3.1534

    authors: Oluwatosin YE,Kane PM

    更新日期:1998-03-01 00:00:00