scholarly journals Correction to: “Activity Suppression Behavior Phenotype in SULT4A1 Frameshift Mutant Zebrafish”

2015 ◽  
Vol 43 (8) ◽  
pp. 1284-1284
Keyword(s):  
Frameshift Mutant

scholarly journals Imbalance between Expression of FOXC2 and Its lncRNA in Lymphedema-Distichiasis Caused by Frameshift Mutations

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 650
Author(s):  
Sara Missaglia ◽  
Daniela Tavian ◽  
Sandro Michelini ◽  
Paolo Enrico Maltese ◽  
Andrea Bonanomi ◽  
...  
Keyword(s):  
Mrna Stability ◽  
Healthy Subjects ◽  
Lymphatic System ◽  
System Development ◽  
Bioinformatic Analysis ◽  
Wild Type ◽  
Mutant Proteins ◽  
Frameshift Mutations ◽  
Forkhead Box ◽  
Frameshift Mutant

Forkhead-box C2 (FOXC2) is a transcription factor involved in lymphatic system development. FOXC2 mutations cause Lymphedema-distichiasis syndrome (LD). Recently, a natural antisense was identified, called lncRNA FOXC2-AS1, which increases FOXC2 mRNA stability. No studies have evaluated FOXC2 and FOXC2-AS1 blood expression in LD and healthy subjects. Here, we show that FOXC2 and FOXC-AS1 expression levels were similar in both controls and patients, and a significantly higher amount of both RNAs was observed in females. A positive correlation between FOXC2 and FOXC2-AS1 expression was found in both controls and patients, excluding those with frameshift mutations. In these patients, the FOXC2-AS1/FOXC2 ratio was about 1:1, while it was higher in controls and patients carrying other types of mutations. The overexpression or silencing of FOXC2-AS1 determined a significant increase or reduction in FOXC2 wild-type and frameshift mutant proteins, respectively. Moreover, confocal and bioinformatic analysis revealed that these variations caused the formation of nuclear proteins aggregates also involving DNA. In conclusion, patients with frameshift mutations presented lower values of the FOXC2-AS1/FOXC2 ratio, due to a decrease in FOXC2-AS1 expression. The imbalance between FOXC2 mRNA and its lncRNA could represent a molecular mechanism to reduce the amount of FOXC2 misfolded proteins, protecting cells from damage.

Evidence That Selected Amplification of a Bacterial lac Frameshift Allele Stimulates Lac+ Reversion (Adaptive Mutation) With or Without General Hypermutability

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 945-956 ◽  
Author(s):  
E Susan Slechta ◽  
Jing Liu ◽  
Dan I Andersson ◽  
John R Roth
Keyword(s):  
Model Selection ◽  
Direct Effect ◽  
Mutation Rate ◽  
Side Effect ◽  
Copy Number ◽  
Fold Increase ◽  
Genetic System ◽  
Adaptive Mutation ◽  
E Coli ◽  
Frameshift Mutant

Abstract In the genetic system of Cairns and Foster, a nongrowing population of an E. coli lac frameshift mutant appears to specifically accumulate Lac+ revertants when starved on medium including lactose (adaptive mutation). This behavior has been attributed to stress-induced general mutagenesis in a subpopulation of starved cells (the hypermutable state model). We have suggested that, on the contrary, stress has no direct effect on mutability but favors only growth of cells that amplify their leaky mutant lac region (the amplification mutagenesis model). Selection enhances reversion primarily by increasing the mutant lac copy number within each developing clone on the selection plate. The observed general mutagenesis is attributed to a side effect of growth with an amplification—induction of SOS by DNA fragments released from a tandem array of lac copies. Here we show that the S. enterica version of the Cairns system shows SOS-dependent general mutagenesis and behaves in every way like the original E. coli system. In both systems, lac revertants are mutagenized during selection. Eliminating the 35-fold increase in mutation rate reduces revertant number only 2- to 4-fold. This discrepancy is due to continued growth of amplification cells until some clones manage to revert without mutagenesis solely by increasing their lac copy number. Reversion in the absence of mutagenesis is still dependent on RecA function, as expected if it depends on lac amplification (a recombination-dependent process). These observations support the amplification mutagenesis model.

scholarly journals Transformation of Neurospora crassa with recombinant plasmids containing the cloned glutamate dehydrogenase (am) gene: evidence for autonomous replication of the transforming plasmid.

1984 ◽  
Vol 4 (10) ◽  
pp. 2041-2051 ◽  
Author(s):  
D M Grant ◽  
A M Lambowitz ◽  
J A Rambosek ◽  
J A Kinsey
Keyword(s):  
Neurospora Crassa ◽  
Glutamate Dehydrogenase ◽  
Tandem Repeats ◽  
Southern Hybridization ◽  
Chromosomal Dna ◽  
Southern Blots ◽  
Recombinant Plasmids ◽  
Frameshift Mutant ◽  
Derivatives Of ◽  
Molecular Weight Form

We have characterized Neurospora crassa transformants obtained with plasmid pJR2, which consists of the Neurospora glutamate dehydrogenase (am) gene cloned in pUC8 and an am132 host strain which contains a deletion encompassing the cloned fragment. Every one of 33 transformants tested showed extreme meiotic instability: less than 1 or 2% am+ progeny were obtained in initial or successive backcrosses between am+ transformants and am132 or in intercrosses between am+ progeny. Furthermore, am+ progeny from backcrosses gave a high proportion of auxotrophic (am) mitotic segregants during vegetative growth. These results indicate that the am+ character is not stably integrated into chromosomal DNA in any of the transformants tested. Nuclear DNAs from six transformants were analyzed by Southern hybridization. All six transformants contained sequences homologous to pJR2. Four showed restriction fragments expected for unmodified pJR2, but most showed additional bands. Southern blots of undigested DNAs showed that the plasmid sequences are present predominantly in high-molecular-weight form (larger than 20 kilobases). Southern blots showed that auxotrophic (am) progeny from a backcross to am132 had lost restriction bands corresponding to free plasmid but retained additional bands, apparently integrated into chromosomal DNA in a nonfunctional manner. Considered together, these results are most reasonably interpreted as follows: recombinant plasmids containing the am+ gene can replicate autonomously in N. crassa, the free plasmids are present in oligomeric or modified form or both, and plasmid sequences also integrate at multiple sites in the deletion host but in a nonfunctional manner. An alternate interpretation--that tandem repeats of the plasmid are integrated into chromosomal DNA but eliminated during meiosis--cannot be completely excluded. However, stable integration of the am gene can be obtained under a variety of other conditions, viz., using the am gene cloned in a phage lambda vector (J. A. Kinsey and J. A. Rambosek, Mol. Cell. Biol. 4:117-122, 1984), using derivatives of pJR2, or using pJR2 to transform a frameshift mutant.

scholarly journals The Cauliflower Mosaic Virus Virion-Associated Protein Is Dispensable for Viral Replication in Single Cells

2002 ◽  
Vol 76 (18) ◽  
pp. 9457-9464 ◽  
Author(s):  
Kappei Kobayashi ◽  
Seiji Tsuge ◽  
Livia Stavolone ◽  
Thomas Hohn
Keyword(s):  
Mosaic Virus ◽  
Single Cells ◽  
Electron Microscopic Examination ◽  
Aphid Transmission ◽  
Cauliflower Mosaic Virus ◽  
Wild Type Virus ◽  
Transmission Factor ◽  
Electron Microscopic ◽  
Additional Function ◽  
Frameshift Mutant

ABSTRACT Cauliflower mosaic virus (CaMV) open reading frame III (ORF III) codes for a virion-associated protein (Vap), which is one of two viral proteins essential for aphid transmission. However, unlike the aphid transmission factor encoded by CaMV ORF II, Vap is also essential for systemic infection, suggesting that it is a multifunctional protein. To elucidate the additional function or functions of Vap, we tested the replication of noninfectious ORF III-defective mutants in transfected turnip protoplasts. PCR and Western blot analyses revealed that CaMV replication had occurred with an efficiency similar to that of wild-type virus and without leading to reversions. Electron microscopic examination revealed that an ORF III frameshift mutant formed normally structured virions. These results demonstrate that Vap is dispensable for replication in single cells and is not essential for virion morphogenesis. Analysis of inoculated turnip leaves showed that the ORF III frameshift mutant does not cause any detectable local infection. These results are strongly indicative of a role for Vap in virus movement.

scholarly journals Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter

1990 ◽  
Vol 10 (11) ◽  
pp. 5747-5752
Author(s):  
J L Evans ◽  
T L Moore ◽  
W M Kuehl ◽  
T Bender ◽  
J P Ting
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Expression Plasmid ◽  
Protein Coding ◽  
Lymphocytic Cell ◽  
Frameshift Mutant ◽  
Myc Gene ◽  
Hybrid Construct ◽  
Myb Protein

The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.

scholarly journals Functional Study of the Retrotransposon-Derived Human PEG10 Protease

2020 ◽  
Vol 21 (7) ◽  
pp. 2424 ◽  
Author(s):  
Mária Golda ◽  
János András Mótyán ◽  
Mohamed Mahdi ◽  
József Tőzsér
Keyword(s):  
Active Site ◽  
Detrimental Effect ◽  
Cellular Proliferation ◽  
Protein Isoforms ◽  
Functional Study ◽  
Aspartic Proteases ◽  
Reading Frame ◽  
Frameshift Mutant ◽  
Pr Domain ◽  
Reading Frames

Paternally expressed gene 10 (PEG10) is a human retrotransposon-derived imprinted gene. The mRNA of PEG10 encodes two protein isoforms: the Gag-like protein (RF1PEG10) is coded by reading frame 1, while the Gag-Pol-like polyprotein (RF1/RF2PEG10) is coded by reading frames 1 and 2. The proteins are translated by a typical retroviral frameshift mechanism. The protease (PR) domain of RF2PEG10 contains an -Asp-Ser-Gly- sequence, which corresponds to the consensus -Asp-Ser/Thr-Gly- active-site motif of retroviral aspartic proteases. The function of the aspartic protease domain of RF2PEG10 remains unclear. To elucidate the function of PEG10 protease (PRPEG10), we designed a frameshift mutant (fsRF1/RF2PEG10) for comparison with the RF1/RF2PEG10 form. To study the effects of PRPEG10 on cellular proliferation and viability, mammalian HEK293T and HaCaT cells were transfected with plasmids coding for either RF1/RF2PEG10, the frameshift mutant (fsRF1/RF2PEG10), or a PR active-site (D370A) mutant fsRF1/RF2PEG10. Our results indicate that fsRF1/RF2PEG10 overexpression results in increased cellular proliferation. Remarkably, transfection with fsRF1/RF2PEG10 had a detrimental effect on cell viability. We hypothesize that PRPEG10 plays an important role in the function of this retroviral remnant, mediating the proliferation of cells and possibly implicating it in the inhibition of apoptosis.

Transformation of Neurospora crassa with recombinant plasmids containing the cloned glutamate dehydrogenase (am) gene: evidence for autonomous replication of the transforming plasmid

1984 ◽  
Vol 4 (10) ◽  
pp. 2041-2051
Author(s):  
D M Grant ◽  
A M Lambowitz ◽  
J A Rambosek ◽  
J A Kinsey
Keyword(s):  
Neurospora Crassa ◽  
Glutamate Dehydrogenase ◽  
Tandem Repeats ◽  
Southern Hybridization ◽  
Chromosomal Dna ◽  
Southern Blots ◽  
Recombinant Plasmids ◽  
Frameshift Mutant ◽  
Derivatives Of ◽  
Molecular Weight Form

We have characterized Neurospora crassa transformants obtained with plasmid pJR2, which consists of the Neurospora glutamate dehydrogenase (am) gene cloned in pUC8 and an am132 host strain which contains a deletion encompassing the cloned fragment. Every one of 33 transformants tested showed extreme meiotic instability: less than 1 or 2% am+ progeny were obtained in initial or successive backcrosses between am+ transformants and am132 or in intercrosses between am+ progeny. Furthermore, am+ progeny from backcrosses gave a high proportion of auxotrophic (am) mitotic segregants during vegetative growth. These results indicate that the am+ character is not stably integrated into chromosomal DNA in any of the transformants tested. Nuclear DNAs from six transformants were analyzed by Southern hybridization. All six transformants contained sequences homologous to pJR2. Four showed restriction fragments expected for unmodified pJR2, but most showed additional bands. Southern blots of undigested DNAs showed that the plasmid sequences are present predominantly in high-molecular-weight form (larger than 20 kilobases). Southern blots showed that auxotrophic (am) progeny from a backcross to am132 had lost restriction bands corresponding to free plasmid but retained additional bands, apparently integrated into chromosomal DNA in a nonfunctional manner. Considered together, these results are most reasonably interpreted as follows: recombinant plasmids containing the am+ gene can replicate autonomously in N. crassa, the free plasmids are present in oligomeric or modified form or both, and plasmid sequences also integrate at multiple sites in the deletion host but in a nonfunctional manner. An alternate interpretation--that tandem repeats of the plasmid are integrated into chromosomal DNA but eliminated during meiosis--cannot be completely excluded. However, stable integration of the am gene can be obtained under a variety of other conditions, viz., using the am gene cloned in a phage lambda vector (J. A. Kinsey and J. A. Rambosek, Mol. Cell. Biol. 4:117-122, 1984), using derivatives of pJR2, or using pJR2 to transform a frameshift mutant.

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