Abstract:
:Pseudo-exons are intronic sequences that are flanked by apparent consensus splice sites but that are not observed in spliced mRNAs. Pseudo-exons are often difficult to activate by mutation and have typically been viewed as a conceptual challenge to our understanding of how the spliceosome discriminates between authentic and cryptic splice sites. We have analyzed an apparent pseudo-exon located downstream of mutually exclusive exons 2 and 3 of the rat alpha-tropomyosin (TM) gene. The TM pseudo-exon is conserved among mammals and has a conserved profile of predicted splicing enhancers and silencers that is more typical of a genuine exon than a pseudo-exon. Splicing of the pseudo-exon is fully activated for splicing to exon 3 by a number of simple mutations. Splicing of the pseudo-exon to exon 3 is predicted to lead to nonsense-mediated decay (NMD). In contrast, when "prespliced" to exon 2 it follows a "zero length exon" splicing pathway in which a newly generated 5' splice site at the junction with exon 2 is spliced to exon 4. We propose that a subset of apparent pseudo-exons, as exemplified here, are actually authentic alternative exons whose inclusion leads to NMD.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Grellscheid SN,Smith CWdoi
10.1128/MCB.26.6.2237-2246.2006subject
Has Abstractpub_date
2006-03-01 00:00:00pages
2237-46issue
6eissn
0270-7306issn
1098-5549pii
26/6/2237journal_volume
26pub_type
杂志文章abstract::EYA1 is known to be overexpressed in human breast cancer, in which the Myc protein is also accumulated in association with decreased phospho-T58 (pT58) levels. We have recently reported that EYA1 functions as a unique protein phosphatase to dephosphorylate Myc at pT58 to regulate Myc levels. However, it remains unclea...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00499-16
更新日期:2016-12-19 00:00:00
abstract::NF-κB activation is a critical component in the transcriptional response to hypoxia. However, the underlying mechanisms that control its activity under these conditions are unknown. Here we report that under hypoxic conditions, IκB kinase (IKK) activity is induced through a calcium/calmodulin-dependent kinase 2 (CaMK2...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00409-10
更新日期:2010-10-01 00:00:00
abstract::Okadaic acid-sensitive serine/threonine phosphatases have been shown to regulate interleukin-2 transcription and T-cell activation. Okadaic acid inhibits protein phosphatase 4 (PP4), a novel PP2A-related serine/threonine phosphatase, at a 50% inhibitory concentration (IC(50)) comparable to that for PP2A. This raises t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00799-06
更新日期:2007-01-01 00:00:00
abstract::Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the nuclear factor of activated T-cell (NFAT) transcription factor but also promotes d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00063-19
更新日期:2019-09-11 00:00:00
abstract::We have used in vitro mutagenesis to examine in detail the roles of two modular protein domains, SH2 and SH3, in the regulation of the Abl tyrosine kinase. As previously shown, the SH3 domain suppresses an intrinsic transforming activity of the normally nontransforming c-Abl product in vivo. We show here that this inh...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.5.2883
更新日期:1994-05-01 00:00:00
abstract::The male-specific-lethal (MSL) proteins in Drosophila melanogaster serve to adjust gene expression levels in male flies containing a single X chromosome to equal those in females with a double dose of X-linked genes. Together with noncoding roX RNA, MSL proteins form the "dosage compensation complex" (DCC), which inte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.14.5947-5954.2005
更新日期:2005-07-01 00:00:00
abstract::TRIF is an essential adaptor for Toll-like receptor 3/4 (TLR3/4) signaling to activate transcription factor interferon regulatory factor 3 (IRF-3). We examined the molecular mechanism of TLR3 signaling and found that TLR3 stimulation by double-stranded RNA (dsRNA) induces phosphorylation of TRIF at Ser210 and is requi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00509-19
更新日期:2020-02-12 00:00:00
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
更新日期:1997-12-01 00:00:00
abstract::Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in integrin-mediated control of cell behavior. Following cell adhesion to components of the extracellular matrix, FAK becomes phosphorylated at multiple sites, including tyrosines 397, 576, and 577. Tyr-397 is an autophosphorylation site tha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.7.4806
更新日期:1999-07-01 00:00:00
abstract::The ∼230-residue C-terminal tail of the epidermal growth factor receptor (EGFR) is phosphorylated upon activation. We examined whether this phosphorylation is affected by deletions within the tail and whether the two tails in the asymmetric active EGFR dimer are phosphorylated differently. We monitored autophosphoryla...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00248-15
更新日期:2015-09-01 00:00:00
abstract::The APN1 gene of Saccharomyces cerevisiae encodes the major apurinic/apyrimidinic endonuclease and 3'-repair DNA diesterase in yeast cell extracts. The Apn1 protein is a homolog of Escherichia coli endonuclease IV, which functions in the repair of some oxidative and alkylation damages in that organism. We show here th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.9.4537
更新日期:1991-09-01 00:00:00
abstract::"Neutropenia" refers to deficient numbers of neutrophils, the most abundant type of white blood cell. Two main forms of inherited neutropenia are cyclic neutropenia, in which neutrophil counts oscillate with a 21-day frequency, and severe congenital neutropenia, in which static neutropenia may evolve at times into leu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00596-09
更新日期:2009-08-01 00:00:00
abstract::The FLP protein of the Saccharomyces cerevisiae plasmid 2 microns circle catalyzes site-specific recombination between two repeated segments present on the plasmid. In this paper we present results of experiments we performed to define more precisely the features of the FLP recognition target site, which we propose to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3357
更新日期:1986-10-01 00:00:00
abstract::Temporal analysis of DNA replication and histone mRNA accumulation in a hamster fibroblast cell cycle mutant (K12) showed that histone mRNA accumulates periodically during the cell cycle and reaches its highest level in the S phase. The direct correlation between the initiation of DNA synthesis and the accumulation of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2364
更新日期:1984-11-01 00:00:00
abstract::Fred Sherman was a prominent yeast geneticist and my mentor in graduate school. Fred passed away in September 2013 at the age of 81. In this minireview, I describe what it was like to know Fred and be in his lab from 1977 to 1982, the extraordinarily exciting time when the recombinant DNA revolution hit yeast genetics...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.01682-13
更新日期:2014-03-01 00:00:00
abstract::The activities of the related Abl and Arg nonreceptor tyrosine kinases are kept under tight control in cells, but exposure to several different stimuli results in a two- to fivefold stimulation of kinase activity. Following the breakdown of inhibitory intramolecular interactions, Abl activation requires phosphorylatio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.11.3884-3896.2003
更新日期:2003-06-01 00:00:00
abstract::SEC63 encodes a protein required for secretory protein translocation into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae (J. A. Rothblatt, R. J. Deshaies, S. L. Sanders, G. Daum, and R. Schekman, J. Cell Biol. 109:2641-2652, 1989). Antibody directed against a recombinant form of the protein detects a 73-kD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.7.3288
更新日期:1992-07-01 00:00:00
abstract::The stem-loop in the 5' untranslated region (UTR) of collagen α1(I) and α2(I) mRNAs (5'SL) is the key element regulating their stability and translation. Stabilization of collagen mRNAs is the predominant mechanism for high collagen expression in fibrosis. LARP6 binds the 5'SL of α1(I) and α2(I) mRNAs with high affini...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05263-11
更新日期:2011-09-01 00:00:00
abstract::Cwc25 has previously been identified to associate with pre-mRNA splicing factor Cef1/Ntc85, a component of the Prp19-associated complex (nineteen complex, or NTC) involved in spliceosome activation. We show here that Cwc25 is neither tightly associated with NTC nor required for spliceosome activation but is required f...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00773-09
更新日期:2009-11-01 00:00:00
abstract::Etoposide, a nonintercalating antitumor drug, is a potent inhibitor of topoisomerase II activity. When Trypanosoma equiperdum is treated with etoposide, cleavable complexes are stabilized between topoisomerase II and kinetoplast DNA minicircles, a component of trypanosome mitochondrial DNA (T. A. Shapiro, V. A. Klein,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.3660
更新日期:1994-06-01 00:00:00
abstract::The yeast protein Spa2p localizes to growth sites and is important for polarized morphogenesis during budding, mating, and pseudohyphal growth. To better understand the role of Spa2p in polarized growth, we analyzed regions of the protein important for its function and proteins that interact with Spa2p. Spa2p interact...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.7.4053
更新日期:1998-07-01 00:00:00
abstract::The Saccharomyces cerevisiae CDC25 gene and closely homologous genes in other eukaryotes encode guanine nucleotide exchange factors for Ras proteins. We have determined the minimal region of the budding yeast CDC25 gene capable of activity in vivo. The region required for full biological activity is approximately 450 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1345
更新日期:1993-03-01 00:00:00
abstract::The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7. In e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.5.881
更新日期:1983-05-01 00:00:00
abstract::Keratins K5 and K14 form the extensive intermediate filament network of mitotically active basal cells in all stratified epithelia. We have explored the regulatory mechanisms governing cell-type-specific and differentiation stage-specific expression of the human K5 gene in transiently transfected keratinocytes in vitr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3176
更新日期:1993-06-01 00:00:00
abstract::Mdm2 and MdmX are structurally related p53-binding proteins that function as critical negative regulators of p53 activity in embryonic and adult tissue. The overexpression of Mdm2 or MdmX inhibits p53 tumor suppressor functions in vitro, and the amplification of Mdm2 or MdmX is observed in human cancers retaining wild...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01108-07
更新日期:2008-02-01 00:00:00
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
更新日期:2014-04-01 00:00:00
abstract::E6-AP is a 100-kDa cellular protein that mediates the interaction of the human papillomavirus type 16 and 18 E6 proteins with p53. The association of p53 with E6 and E6-AP promotes the specific ubiquitination and subsequent proteolytic degradation of p53 in vitro. We recently isolated a cDNA encoding E6-AP and have no...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.8.4918
更新日期:1993-08-01 00:00:00
abstract::The inducible transcriptional complex AP-1, composed of c-Fos and c-Jun proteins, is crucial for cell adaptation to many environmental changes. While its mechanisms of activation have been extensively studied, how its activity is restrained is poorly understood. We report here that lysine 265 of c-Fos is conjugated by...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.16.6964-6979.2005
更新日期:2005-08-01 00:00:00
abstract::Up to 70% of human genes are associated with regions of nonmethylated DNA called CpG islands (S. Saxonov, P. Berg, and D. L. Brutlag, Proc. Natl. Acad. Sci. U. S. A. 103:1412-1417, 2006). Usually associated with the 5' end of genes, CpG islands are thought to impact gene expression. We previously demonstrated that the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06332-11
更新日期:2012-01-01 00:00:00
abstract::The human fetal G gamma-globin and adult beta-globin genes are expressed in a tissue- and developmental stage-specific pattern in transgenic mice: the G gamma gene in embryonic cells and the beta gene in fetal and adult erythroid cells. Several of the cis-acting DNA sequences thought to be responsible for these patter...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.1116
更新日期:1990-03-01 00:00:00