Abstract:
:Although globin mRNAs are considered prototypes of highly stable messages, the mechanisms responsible for their longevity remain largely undefined. As an initial step in identifying potential cis-acting elements or structures which contribute to their stability, we analyzed the defect in expression of a naturally occurring alpha 2-globin mutant, alpha Constant Spring (CS). The CS mutation is a single-base change in the translation termination codon (UAA-->CAA) that allows the ribosome to read through into the 3' nontranslated region (NTR). The presence of CS mRNA in transcriptionally active erythroid precursors and its absence (relative to normal alpha-globin mRNA) in the more differentiated transcriptionally silent erythrocytes suggest that this mutation disrupts some feature of the alpha-globin mRNA required for its stability. Using a transient transfection system, we demonstrate that in murine erythroleukemia cells the CS mRNA is unstable compared with the normal alpha 2-globin mRNA. The analyses of several other naturally occurring and site-directed mutant alpha-globin genes in murine erythroleukemia cells indicate that entry of a translating ribosome into the 3' NTR targets the message for accelerated degradation in erythroid cells. In contrast, both the CS and alpha 2-globin mRNAs are stable in several nonerythroid cell lines. These results suggest that translational readthrough disrupts a determinant associated with the alpha 2-globin 3' NTR which is required for mRNA stability in erythroid cells.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Weiss IM,Liebhaber SAdoi
10.1128/mcb.14.12.8123subject
Has Abstractpub_date
1994-12-01 00:00:00pages
8123-32issue
12eissn
0270-7306issn
1098-5549journal_volume
14pub_type
杂志文章abstract::Protein acetylation has emerged as a means of controlling levels of mRNA synthesis in eukaryotic cells. Here we report that acetyl coenzyme A (acetyl-CoA) stimulates RNA polymerase II transcription in vitro in the absence of histones. The effect of acetyl-CoA on basal and activated transcription was studied in a human...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.6.1923-1930.2000
更新日期:2000-03-01 00:00:00
abstract::Cancer cells often heavily depend on the ubiquitin-proteasome system (UPS) for their growth and survival. Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors. A major cause of this resistance is the proteasome boun...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00252-18
更新日期:2018-08-15 00:00:00
abstract::To characterize further the regulatory mechanism modulating the expression of the Saccharomyces cerevisiae ARG3 gene, i.e., the specific repression by arginine and the general amino acid control, we analyzed by deletion the region upstream of that gene, determined the nucleotide sequence of operator-constitutive-like ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.11.3139
更新日期:1985-11-01 00:00:00
abstract::Secretory proteins in eukaryotic cells are transported to the cell surface via the endoplasmic reticulum (ER) and the Golgi apparatus by membrane-bounded vesicles. We screened a collection of temperature-sensitive mutants of Saccharomyces cerevisiae for defects in ER-to-Golgi transport. Two of the genes identified in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.12.7139
更新日期:1998-12-01 00:00:00
abstract::In eukaryotic cells, calcium entry across the cell surface activates nuclear gene expression, a process critically important for cell growth and differentiation, learning, and memory and immune cell functions. In immune cells, calcium entry occurs through store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01068-14
更新日期:2015-04-01 00:00:00
abstract::Activation of PERK following the accumulation of unfolded proteins in the endoplasmic reticulum (ER) promotes translation inhibition and cell cycle arrest. PERK function is essential for cell survival following exposure of cells to ER stress, but the mechanisms whereby PERK signaling promotes cell survival are not tho...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.20.7198-7209.2003
更新日期:2003-10-01 00:00:00
abstract::Spatial control of cytokinesis is essential for proper cell division. The molecular mechanisms that anchor the dynamic assembly and constriction of the cytokinetic ring at the plasma membrane remain unclear. In the fission yeast Schizosaccharomyces pombe, the cytokinetic ring is assembled in the cell middle from corti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01286-12
更新日期:2013-01-01 00:00:00
abstract::It is well accepted that for transcriptional silencing in budding yeast, the evolutionarily conserved lysine deacetylase Sir2, in concert with its partner proteins Sir3 and Sir4, establishes a chromatin structure that prevents RNA polymerase II (Pol II) transcription. However, the mechanism of repression remains contr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00019-08
更新日期:2008-06-01 00:00:00
abstract::The cardiac troponin C (cTnC) gene produces identical transcripts in slow-twitch skeletal muscle and in heart muscle (R. Gahlmann, R. Wade, P. Gunning, and L. Kedes, J. Mol. Biol. 201:379-391, 1988). A separate gene encodes the fast-twitch skeletal muscle troponin C and is not expressed in heart muscle. We have used t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.11.6752
更新日期:1993-11-01 00:00:00
abstract::Spermatogonial stem cells (SSCs) are unipotent germ cells that are at the foundation of spermatogenesis and male fertility. However, the underlying molecular mechanisms governing SSC stemness and growth properties remain elusive. We have recently identified chromodomain helicase/ATPase DNA binding protein 1-like (Chd1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00357-18
更新日期:2019-02-04 00:00:00
abstract::The MyoD family of basic helix-loop-helix transcription factors function as heterodimers with members of the E-protein family to induce myogenic gene activation. The E-protein HEB is alternatively spliced to generate alpha and beta isoforms. While the function of these molecules has been studied in other cell types, q...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02404-05
更新日期:2006-08-01 00:00:00
abstract::It is well established that cell survival signals stimulated by growth factors, cytokines, and oncoproteins are initiated by phosphoinositide 3-kinase (PI3K)- and Akt-dependent signal transduction pathways. Oncogenic Ras, an upstream activator of Akt, requires NF-kappaB to initiate transformation, at least partially t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.5.1626-1638.2000
更新日期:2000-03-01 00:00:00
abstract::Injection of transcription activator-like effector nucleases (TALEN) mRNAs into mouse zygotes transferred into foster mothers efficiently generated founder mice with heritable mutations in targeted genes. Immunofluorescence visualization of phosphorylated histone 2A (γH2AX) combined with fluorescence in situ hybridiza...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00023-14
更新日期:2014-05-01 00:00:00
abstract::The mouse myosin light-chain 1A (MLC1A) gene, expressed in the atria of the adult heart, is one of the first muscle genes to be activated when skeletal as well as cardiac muscles form in the embryo. It is also transcribed in skeletal muscle cell lines at the onset of differentiation. Transient transfection assays of m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4585
更新日期:1995-08-01 00:00:00
abstract::Genetic and biochemical evidence suggests that the Ras protooncogene product regulates the activation of the Raf kinase pathway, leading to the proposal that Raf is a direct mitogenic effector of activated Ras. Here we report the use of a novel competition assay to measure in vitro the relative affinity of the c-Raf-1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.8.5318
更新日期:1994-08-01 00:00:00
abstract::The mTOR signaling complex integrates signals from growth factors and nutrient availability to control cell growth and proliferation, in part through effects on the protein-synthetic machinery. Protein synthesis rates fluctuate throughout the cell cycle but diminish significantly during the G(2)/M transition. The fate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00322-09
更新日期:2010-07-01 00:00:00
abstract::Fms is the receptor for macrophage colony-stimulating factor (M-CSF) and contains intrinsic tyrosine kinase activity. Expression of exogenous Fms in a murine myeloid progenitor cell line, FDC-P1 (FD-Fms), results in M-CSF-dependent growth and macrophage differentiation. Previously, we described a 100-kDa protein that ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.9.3047-3056.2001
更新日期:2001-05-01 00:00:00
abstract::A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3' untranslated region (3' UTR)....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.12.4265-4274.2000
更新日期:2000-06-01 00:00:00
abstract::Eukaryotic viruses have devised numerous strategies to downregulate activity of the interferon-induced, double-stranded (dsRNA)-activated protein kinase (referred to as p68 on the basis of its Mr of 68,000 in human cells). Viruses must exert this control to avoid extensive phosphorylation of the alpha subunit of eukar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.11.5497
更新日期:1991-11-01 00:00:00
abstract::Double-stranded RNA (dsRNA) accumulates in virus-infected mammalian cells and signals the activation of host defense pathways of the interferon system. We describe here a novel form of dsRNA-triggered signaling that leads to the stimulation of the p38 mitogen-activated protein kinase (p38 MAPK) and the c-Jun NH(2)-ter...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.2.617-627.2000
更新日期:2000-01-01 00:00:00
abstract::The molecular chaperone HSP90 regulates stability and function of multiple protein kinases. The HSP90-binding drug geldanamycin interferes with this activity and promotes proteasome-dependent degradation of most HSP90 client proteins. Geldanamycin also binds to GRP94, the HSP90 paralog located in the endoplasmic retic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.24.8506-8513.2002
更新日期:2002-12-01 00:00:00
abstract::We previously observed that nitric oxide (NO) exposure increases the stability of mRNAs encoding heme oxygenase 1 (HO-1) and TIEG-1 in human and mouse fibroblasts. Here, we have used microarrays to look broadly for changes in mRNA stability in response to NO treatment. Using human IMR-90 and mouse NIH 3T3 fibroblasts ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01495-08
更新日期:2009-05-01 00:00:00
abstract::The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicke...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.5756
更新日期:1994-09-01 00:00:00
abstract::LFB1 (HNF1) is a tissue-specific transcription factor found in the livers, stomachs, intestines, and kidneys of vertebrates. By analyzing the promoter of the Xenopus LFB1 gene, we identified potential autoregulation by LFB1 and regulation by HNF4, a transcription factor with a tissue distribution similar to that of LF...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6416
更新日期:1993-10-01 00:00:00
abstract::The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deleti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.7.2661-2674.2006
更新日期:2006-04-01 00:00:00
abstract::The chemotropic guidance cue netrin-1 mediates attraction of migrating axons during central nervous system development through the receptor Deleted in Colorectal Cancer (DCC). Downstream of netrin-1, activated Rho GTPases Rac1 and Cdc42 induce cytoskeletal rearrangements within the growth cone. The Rho guanine nucleot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01264-12
更新日期:2013-02-01 00:00:00
abstract::We sought to study the binding constraints placed on the nine-zinc-finger protein transcription factor IIIA (TFIIIA) by a histone octamer. To this end, five overlapping fragments of the Xenopus laevis oocyte and somatic 5S rRNA genes were reconstituted into nucleosomes, and it was subsequently shown that nucleosome tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.3.1156
更新日期:1998-03-01 00:00:00
abstract::The Integrator Complex is a group of proteins responsible for the endonucleolytic cleavage of primary small nuclear RNA (snRNA) transcripts within the nucleus. Integrator subunits 9 and 11 (IntS9/11) are thought to contain the catalytic activity based on their high sequence similarity to CPSF100 and CPSF73, which have...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06511-11
更新日期:2012-03-01 00:00:00
abstract::Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.2.1095
更新日期:1994-02-01 00:00:00
abstract::The expression of the chicken delta 1-crystallin gene is primarily regulated by the action of a lens-specific enhancer 1 kilobase long and located in the third intron of the gene (S. Hayashi, K. Goto, T. S. Okada, and H. Kondoh, Genes Dev. 1:818-828, 1987). The 120-base-long core segment is required for the activity o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.958
更新日期:1990-03-01 00:00:00