Abstract:
:RNase H1 in mammalian cells is present in nuclei and mitochondria. Its absence in mitochondria results in embryonic lethality due to the failure to amplify mitochondrial DNA (mtDNA). Dual localization to mitochondria and nuclei results from differential translation initiation at two in-frame AUGs (M1 and M27) of a single mRNA. Here we show that expression levels of the two isoforms depend on the efficiency of translation initiation at each AUG codon and on the presence of a short upstream open reading frame (uORF) resulting in the mitochondrial isoform being about 10% as abundant as the nuclear form. Translation initiation at the M1 AUG is restricted by the uORF, while expression of the nuclear isoform requires reinitiation of ribosomes at the M27 AUG after termination of uORF translation or new initiation by ribosomes skipping the uORF and the M1 AUG. Such translational organization of RNase H1 allows tight control of expression of RNase H1 in mitochondria, where its excess or absence can lead to cell death, without affecting the expression of the nuclear RNase H1.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Suzuki Y,Holmes JB,Cerritelli SM,Sakhuja K,Minczuk M,Holt IJ,Crouch RJdoi
10.1128/MCB.00619-10subject
Has Abstractpub_date
2010-11-01 00:00:00pages
5123-34issue
21eissn
0270-7306issn
1098-5549pii
MCB.00619-10journal_volume
30pub_type
杂志文章abstract::Loss of p53 sensitizes to antimicrotubule agents in human tumor cells, but little is known about its role during mitosis. We have identified the Polo-like kinase family member serum inducible kinase (Snk/Plk2) as a novel p53 target gene. Snk/Plk2 mutagenesis demonstrated that its kinase activity is negatively regulate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.16.5556-5571.2003
更新日期:2003-08-01 00:00:00
abstract::This is the first study reporting the inactivation of a member of the mouse gene family of toxin-related ecto-ADP-ribosyltransferases (ARTs). Transfer of the ADP-ribose moiety from NAD onto extracellular arginine residues on T-cell membrane proteins is mediated by glycosylphosphatidylinositol-linked cell surface ARTs....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.21.7535-7542.2002
更新日期:2002-11-01 00:00:00
abstract::The fucose alpha(1-->2) galactose beta structure is expressed by uterine epithelial cells in the mouse and has been implicated in blastocyst adhesion events thought to be required for murine implantation. Fucalpha(1-->2)Galbeta moieties and cognate fucosyltransferases are also expressed by epithelial cells of the male...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.24.8336-8345.2001
更新日期:2001-12-01 00:00:00
abstract::2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17beta-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent deg...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.6.1843-1855.2003
更新日期:2003-03-01 00:00:00
abstract::Though widely recognized in higher eukaryotes, the regulation of Saccharomyces cerevisiae genes transcribed by RNA polymerase II by proteins that bind within the coding sequence remains largely speculative. We have shown for the LPD1 gene, encoding lipoamide dehydrogenase, that the coding sequence between +13 and +469...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.214
更新日期:1994-01-01 00:00:00
abstract::We introduced a human beta-globin gene into murine erythroleukemia (MEL) cells by infection with recombinant retroviruses containing the complete genomic globin sequence. The beta-globin gene was correctly regulated during differentiation, steady-state mRNA levels being induced 5- to 30-fold after treatment of the cel...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.2.887
更新日期:1987-02-01 00:00:00
abstract::T cell antigen receptor (TCR) activation triggers profound changes in the actin cytoskeleton. In addition to controlling cellular shape and polarity, this process regulates vital T cell responses, such as T cell adhesion, motility, and proliferation. These depend on the recruitment of the signaling proteins Nck and Wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01358-10
更新日期:2011-07-01 00:00:00
abstract::The mammalian signal recognition particle (SRP) is a small cytoplasmic ribonucleoprotein required for the cotranslational targeting of secretory proteins to the endoplasmic reticulum membrane. The heterodimeric protein subunit SRP9/14 was previously shown to be essential for SRP to cause pausing in the elongation of s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.8.3949
更新日期:1991-08-01 00:00:00
abstract::RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00560-08
更新日期:2008-10-01 00:00:00
abstract::All inbred strains of mice carry the Ren-1 structural gene, which encodes the renin-1 isozyme, the classical renin activity found in kidneys. In addition, some strains carry a second renin structural gene, Ren-2, which encodes the predominantly expressed submaxillary gland renin isozyme, renin-2. Ren-1 and Ren-2 exhib...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2321
更新日期:1984-11-01 00:00:00
abstract::Centrins in vertebrates have traditionally been associated with microtubule-nucleating centers such as the centrosome. Unexpectedly, we found centrin 2 to associate biochemically with nucleoporins, including the Xenopus laevis Nup107-160 complex, a critical subunit of the vertebrate nuclear pore in interphase and of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01697-07
更新日期:2008-03-01 00:00:00
abstract::We have isolated and subcloned three separate segments of human DNA which share strong sequence homology with a previously sequenced gene encoding a type I keratin, K14 (50 kilodaltons). Restriction endonuclease mapping has demonstrated that these three genes are tightly linked chromosomally, whereas the K14 gene appe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.539
更新日期:1986-02-01 00:00:00
abstract::NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.12.5929
更新日期:1991-12-01 00:00:00
abstract::The Saccharomyces cerevisiae mutant ref2-1 (REF = RNA end formation) was originally identified by a genetic strategy predicted to detect decreases in the use of a CYC1 poly(A) site interposed within the intron of an ACT1-HIS4 fusion reporter gene. Direct RNA analysis now proves this effect and also demonstrates the tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.3.1689
更新日期:1995-03-01 00:00:00
abstract::The pocket protein family of tumor suppressors, and Rb specifically, have been implicated as controlling terminal differentiation in many tissues, including the heart. To establish the biological functions of Rb in the heart and overcome the early lethality caused by germ line deletion of Rb, we used a Cre/loxP system...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.6.2486-2497.2005
更新日期:2005-03-01 00:00:00
abstract::Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes. When a cell detects damaged DNA, Rad53 activity is dramatically increased, which ultimately leads to changes in DNA replication, repair, and cell division. Despite its central role in checkpoint signal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.10.3405-3416.2003
更新日期:2003-05-01 00:00:00
abstract::The Caenorhabditis elegans run gene encodes a Runt domain factor. Runx1, Runx2, and Runx3 are the three known mammalian homologs of run. Runx1, which plays an essential role in hematopoiesis, has been identified at the breakpoint of chromosome translocations that are responsible for human leukemia. Runx2 plays an esse...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.2.547-554.2002
更新日期:2002-01-01 00:00:00
abstract::Recent results have shown that the ability of farnesyltransferase inhibitors (FTIs) to inhibit malignant cell transformation and Ras prenylation can be separated. We proposed previously that farnesylated Rho proteins are important targets for alternation by FTIs, based on studies of RhoB (the FTI-Rho hypothesis). Cell...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.3.1831
更新日期:1999-03-01 00:00:00
abstract::SLC5A8 is a putative tumor suppressor that is inactivated in more than 10 different types of cancer, but neither the oncogenic signaling responsible for SLC5A8 inactivation nor the functional relevance of SLC5A8 loss to tumor growth has been elucidated. Here, we identify oncogenic HRAS (HRAS(G12V)) as a potent mediato...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01702-12
更新日期:2013-10-01 00:00:00
abstract::In Schizosaccharomyces pombe, MBF is a DNA-binding complex suspected to activate the transcription of genes necessary for entry into S phase. The MBF complex contains both p85cdc10 and p72res1/sct1. To obtain a better understanding of how the MBF complex regulates gene expression at the G1/S transition, we have perfor...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.5.2589
更新日期:1995-05-01 00:00:00
abstract::An accumulation in cells of unfolded proteins is believed to be the common signal triggering the induction of heat shock proteins (hsps). Accordingly, in Saccharomyces cerevisiae, inhibition of protein breakdown at 30 degrees C with the proteasome inhibitor MG132 caused a coordinate induction of many heat shock protei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.30
更新日期:1998-01-01 00:00:00
abstract::We have recently reported that the yeast chromatin-remodeling factor Swi1 can exist as a prion, [SWI(+)], demonstrating a link between prionogenesis and global transcriptional regulation. To shed light on how the Swi1 conformational switch influences Swi1 function and to define the sequence and structural requirements...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00225-10
更新日期:2010-10-01 00:00:00
abstract::Endonuclease decay of nonsense-containing beta-globin mRNA in erythroid cells generates 5'-truncated products that were reported previously to have a cap or caplike structure. We confirmed that this 5' modification is indistinguishable from the cap on full-length mRNA, and Western blotting, immunoprecipitation, and ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01325-08
更新日期:2009-04-01 00:00:00
abstract::The HOG (high-osmolarity glycerol) mitogen-activated protein kinase (MAPK) pathway regulates the osmotic stress response in the yeast Saccharomyces cerevisiae. Three type 2C Ser/Thr phosphatases (PTCs), Ptc1, Ptc2, and Ptc3, have been isolated as negative regulators of this pathway. Previously, multicopy expression of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.1.51-60.2001
更新日期:2001-01-01 00:00:00
abstract::Using the method of chromosomal walking, we have isolated a contiguous region of the Drosophila melanogaster X chromosome which corresponds to salivary gland chromosome bands 3C12 to 3D4. This five-band region contains approximately 100 kilobases of DNA, including those sequences comprising dunce, a gene which functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.2.358
更新日期:1984-02-01 00:00:00
abstract::Telomere stabilization is critical for tumorigenesis. A number of tumors and cell lines use a recombination-based mechanism, alternative lengthening of telomeres (ALT), to maintain telomere repeat arrays. Current data suggest that the mutation of p53 facilitates the activation of this pathway. In addition to its funct...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.13.5967-5977.2004
更新日期:2004-07-01 00:00:00
abstract::To determine whether regulation of c-myc proteins occurs during the differentiation of murine erythroleukemia cells, we examined c-myc protein synthesis and accumulation throughout dimethyl sulfoxide (DMSO)- or hypoxanthine-induced differentiation. c-myc protein expression exhibited an overall biphasic reduction, with...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.8.3952
更新日期:1990-08-01 00:00:00
abstract::Protein kinase activities were measured in Rous sarcoma virus-infected baby hamster kidney (BHK) cells that express v-src (BHK [v-src]) and compared with those of revertant and control BHK cells. We observed about a fivefold-higher tyrosine phosphorylating activity in BHK (v-src) cell extracts, which was due to src bu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.5.973
更新日期:1984-05-01 00:00:00
abstract::The transcription factor hepatocyte nuclear factor 3 (HNF-3) is involved in the coordinate expression of several liver genes. HNF-3 DNA binding activity is composed of three different liver proteins which recognize the same DNA site. The HNF-3 proteins (designated alpha, beta, and gamma) possess homology in the DNA bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.2.552
更新日期:1992-02-01 00:00:00
abstract::Expression of the acute-phase response genes, such as that for alpha-1 acid glycoprotein (AGP), involves both positive and negative transcription factors. A positive transcription factor, AGP/EBP, and a negative transcription factor, factor B, have been identified as the two most important factors responsible for the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6068
更新日期:1994-09-01 00:00:00