scholarly journals Targeted Long-Read Sequencing Decodes the Transcriptional Atlas of the Founding RAS Gene Family Members

2021 ◽  
Vol 22 (24) ◽  
pp. 13298
Author(s):  
Panagiotis G. Adamopoulos ◽  
Panagiotis Tsiakanikas ◽  
Michaela A. Boti ◽  
Andreas Scorilas
Keyword(s):  
Gene Family ◽  
Expression Profiles ◽  
Protein Isoforms ◽  
Alternative Transcript ◽  
Transcriptional Level ◽  
Ras Gene ◽  
Ras Genes ◽  
Transcript Variants ◽  
Depth Analysis ◽  
Genes Encoding

The complicity of human RAS proteins in cancer is a well-documented fact, both due to the mutational hyperactivation of these GTPases and the overexpression of the genes encoding these proteins. Thus, it can be easily assumed that the study of RAS genes at the transcriptional and post-transcriptional level is of the utmost importance. Although previous research has shed some light on the basic mechanisms by which GTPases are involved in tumorigenesis, limited information is known regarding the transcriptional profile of the genes encoding these proteins. The present study highlights for the first time the wide spectrum of the mRNAs generated by the three most significant RAS genes (KRAS, NRAS and HRAS), providing an in-depth analysis of the splicing events and exon/intron boundaries. The implementation of a versatile, targeted nanopore-sequencing approach led to the identification of 39 novel RAS mRNA transcript variants and to the elucidation of their expression profiles in a broad panel of human cell lines. Although the present work unveiled multiple hidden aspects of the RAS gene family, further study is required to unravel the biological function of all the novel alternative transcript variants, as well as the putative protein isoforms.

scholarly journals Nanopore Sequencing Unveils Diverse Transcript Variants of the Epithelial Cell-Specific Transcription Factor Elf-3 in Human Malignancies

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 839
Author(s):  
Michaela A. Boti ◽  
Panagiotis G. Adamopoulos ◽  
Panagiotis Tsiakanikas ◽  
Andreas Scorilas
Keyword(s):  
Transcription Factor ◽  
Epithelial Cell ◽  
Wide Spectrum ◽  
Protein Isoforms ◽  
Alternative Transcript ◽  
Nanopore Sequencing ◽  
Transcript Variants ◽  
Mesenchymal To Epithelial Transition ◽  
Depth Analysis ◽  
Ets Family

The human E74-like ETS transcription factor 3 (Elf-3) is an epithelium-specific member of the ETS family, all members of which are characterized by a highly conserved DNA-binding domain. Elf-3 plays a crucial role in epithelial cell differentiation by participating in morphogenesis and terminal differentiation of the murine small intestinal epithelium, and also acts as an indispensable regulator of mesenchymal to epithelial transition, underlying its significant involvement in development and in pathological states, such as cancer. Although previous research works have deciphered the functional role of Elf-3 in normal physiology as well as in tumorigenesis, the present study highlights for the first time the wide spectrum of ELF3 mRNAs that are transcribed, providing an in-depth analysis of splicing events and exon/intron boundaries in a broad panel of human cell lines. The implementation of a versatile targeted nanopore sequencing approach led to the identification of 25 novel ELF3 mRNA transcript variants (ELF3 v.3–v.27) with new alternative splicing events, as well as two novel exons. Although the current study provides a qualitative transcriptional profile regarding ELF3, further studies must be conducted, so the biological function of all novel alternative transcript variants as well as the putative protein isoforms are elucidated.

Saccharomyces cerevisiae synthesizes proteins related to the p21 gene product of ras genes found in mammals

1984 ◽  
Vol 4 (1) ◽  
pp. 23-29
Author(s):  
A G Papageorge ◽  
D Defeo-Jones ◽  
P Robinson ◽  
G Temeles ◽  
E M Scolnick
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Family ◽  
Yeast Cells ◽  
Drosophila Genome ◽  
Ras Gene ◽  
Rat Serum ◽  
Viral Oncogenes ◽  
Ras Genes ◽  
Family Based ◽  
Related Proteins

A family of normal vertebrate genes and oncogenes has been called the ras gene family. The name ras was assigned to this gene family based on the species of origin of the viral oncogenes of the rat-derived Harvey and Kirsten murine sarcoma viruses. There are now three known functional members of the ras gene family, and genes homologous to ras genes have been detected in the DNA of a wide variety of mammals and in Drosophila melanogaster. Prior experiments have detected proteins coded for by ras genes in a large number of normal cells, cell lines, and tumors. We report here the detection of ras-related proteins in D. melanogaster, a result predicted by the earlier detection of ras-related genes in the Drosophila genome. We also report for the first time the detection of ras-related proteins in a single-cell eucaryocyte, Saccharomyces cerevisiae. These proteins, approximately 30K in size, are recognized by both a monoclonal antibody which binds to the p21 coded for by mammalian ras genes and a polyclonal rat serum made by transplanting a v-Ha-ras-induced tumor in Osborne-Mendel rats. The p21 of v-Ha-ras and the 30K proteins from S. cerevisiae share methionine-labeled peptides as detected by two-dimensional tryptic peptide maps. The results indicate that S. cerevisiae synthesizes ras-related proteins. A genetic analysis of the function of these proteins for yeast cells may now be possible.

scholarly journals Expression of ZNF695 Transcript Variants in Childhood B-Cell Acute Lymphoblastic Leukemia

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 716 ◽  
Author(s):  
Rosa ◽  
Villegas-Ruíz ◽  
Caballero-Palacios ◽  
Pérez-López ◽  
Murata ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Alternative Transcript ◽  
Human Transcriptome ◽  
Transcript Variants ◽  
Cell Acute Lymphoblastic Leukemia

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for 2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

scholarly journals Characterization of the Brassica napus Flavonol Synthase Gene Family Reveals Bifunctional Flavonol Synthases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanna Marie Schilbert ◽  
Maximilian Schöne ◽  
Thomas Baier ◽  
Mareike Busche ◽  
Prisca Viehöver ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Gene Family ◽  
Expression Profiles ◽  
Reproductive Organs ◽  
In Planta ◽  
Flavonol Synthase ◽  
Genes Encoding ◽  
Key Enzyme ◽  
Spatio Temporal

Flavonol synthase (FLS) is a key enzyme for the formation of flavonols, which are a subclass of the flavonoids. FLS catalyzes the conversion of dihydroflavonols to flavonols. The enzyme belongs to the 2-oxoglutarate-dependent dioxygenases (2-ODD) superfamily. We characterized the FLS gene family of Brassica napus that covers 13 genes, based on the genome sequence of the B. napus cultivar Express 617. The goal was to unravel which BnaFLS genes are relevant for seed flavonol accumulation in the amphidiploid species B. napus. Two BnaFLS1 homeologs were identified and shown to encode bifunctional enzymes. Both exhibit FLS activity as well as flavanone 3-hydroxylase (F3H) activity, which was demonstrated in vivo and in planta. BnaFLS1-1 and -2 are capable of converting flavanones into dihydroflavonols and further into flavonols. Analysis of spatio-temporal transcription patterns revealed similar expression profiles of BnaFLS1 genes. Both are mainly expressed in reproductive organs and co-expressed with the genes encoding early steps of flavonoid biosynthesis. Our results provide novel insights into flavonol biosynthesis in B. napus and contribute information for breeding targets with the aim to modify the flavonol content in rapeseed.

Differential expression of the ras gene family in mice

1987 ◽  
Vol 7 (4) ◽  
pp. 1535-1540 ◽  
Author(s):  
J Leon ◽  
I Guerrero ◽  
A Pellicer
Keyword(s):  
Gene Family ◽  
Differential Expression ◽  
Adult Mouse ◽  
Expression Patterns ◽  
Cellular Functions ◽  
Ras Gene ◽  
Ras Genes ◽  
Mouse Tissues

We compared the expression of the ras gene family (H-ras, K-ras, and N-ras) in adult mouse tissues and during development. We found substantial variations in expression among different organs and in the amounts of the different transcripts originating from each gene, especially for the N-ras gene. The expression patterns were consistent with the reported preferential tissue activation of ras genes and suggested different cellular functions for each of the ras genes.

scholarly journals Saccharomyces cerevisiae synthesizes proteins related to the p21 gene product of ras genes found in mammals.

1984 ◽  
Vol 4 (1) ◽  
pp. 23-29 ◽  
Author(s):  
A G Papageorge ◽  
D Defeo-Jones ◽  
P Robinson ◽  
G Temeles ◽  
E M Scolnick
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Family ◽  
Yeast Cells ◽  
Drosophila Genome ◽  
Ras Gene ◽  
Rat Serum ◽  
Viral Oncogenes ◽  
Ras Genes ◽  
Family Based ◽  
Related Proteins

A family of normal vertebrate genes and oncogenes has been called the ras gene family. The name ras was assigned to this gene family based on the species of origin of the viral oncogenes of the rat-derived Harvey and Kirsten murine sarcoma viruses. There are now three known functional members of the ras gene family, and genes homologous to ras genes have been detected in the DNA of a wide variety of mammals and in Drosophila melanogaster. Prior experiments have detected proteins coded for by ras genes in a large number of normal cells, cell lines, and tumors. We report here the detection of ras-related proteins in D. melanogaster, a result predicted by the earlier detection of ras-related genes in the Drosophila genome. We also report for the first time the detection of ras-related proteins in a single-cell eucaryocyte, Saccharomyces cerevisiae. These proteins, approximately 30K in size, are recognized by both a monoclonal antibody which binds to the p21 coded for by mammalian ras genes and a polyclonal rat serum made by transplanting a v-Ha-ras-induced tumor in Osborne-Mendel rats. The p21 of v-Ha-ras and the 30K proteins from S. cerevisiae share methionine-labeled peptides as detected by two-dimensional tryptic peptide maps. The results indicate that S. cerevisiae synthesizes ras-related proteins. A genetic analysis of the function of these proteins for yeast cells may now be possible.

scholarly journals CO2-Responsive Expression and Gene Organization of Three Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Enzymes and Carboxysomes in Hydrogenovibrio marinus Strain MH-110

2004 ◽  
Vol 186 (17) ◽  
pp. 5685-5691 ◽  
Author(s):  
Yoichi Yoshizawa ◽  
Koichi Toyoda ◽  
Hiroyuki Arai ◽  
Masaharu Ishii ◽  
Yasuo Igarashi
Keyword(s):  
Expression Profiles ◽  
Electron Microscopic Observation ◽  
Gene Organization ◽  
Transcriptional Level ◽  
Electron Microscopic ◽  
Bisphosphate Carboxylase ◽  
Reverse Transcription Pcr ◽  
Different Types ◽  
Genes Encoding

ABSTRACT Hydrogenovibrio marinus strain MH-110, an obligately lithoautotrophic hydrogen-oxidizing bacterium, fixes CO2 by the Calvin-Benson-Bassham cycle. Strain MH-110 possesses three different sets of genes for ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO): CbbLS-1 and CbbLS-2, which belong to form I (L8S8), and CbbM, which belongs to form II (Lx). In this paper, we report that the genes for CbbLS-1 (cbbLS-1) and CbbM (cbbM) are both followed by the cbbQO genes and preceded by the cbbR genes encoding LysR-type regulators. In contrast, the gene for CbbLS-2 (cbbLS-2) is followed by genes encoding carboxysome shell peptides. We also characterized the three RubisCOs in vivo by examining their expression profiles in environments with different CO2 availabilities. Immunoblot analyses revealed that when strain MH-110 was cultivated in 15% CO2, only the form II RubisCO, CbbM, was expressed. When strain MH-110 was cultivated in 2% CO2, CbbLS-1 was expressed in addition to CbbM. In the 0.15% CO2 culture, the expression of CbbM decreased and that of CbbLS-1 disappeared, and CbbLS-2 was expressed. In the atmospheric CO2 concentration of approximately 0.03%, all three RubisCOs were expressed. Transcriptional analyses of mRNA by reverse transcription-PCR showed that the regulation was at the transcriptional level. Electron microscopic observation of MH-110 cells revealed the formation of carboxysomes in the 0.15% CO2 concentration. The results obtained here indicate that strain MH-110 adapts well to various CO2 concentrations by using different types of RubisCO enzymes.

scholarly journals Characterization of the Brassica napus flavonol synthase gene family reveals bifunctional flavonol synthases

2021 ◽  
Author(s):  
Hanna Marie Schilbert ◽  
Maximilian Schoene ◽  
Thomas Baier ◽  
Mareike Busche ◽  
Prisca Viehoever ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Gene Family ◽  
Expression Profiles ◽  
Reproductive Organs ◽  
In Planta ◽  
Flavonol Synthase ◽  
Genes Encoding ◽  
Key Enzyme ◽  
Spatio Temporal

Flavonol synthase (FLS) is a key enzyme for the formation of flavonols, which are a subclass of the flavonoids. FLS catalyses the conversion of dihydroflavonols to flavonols. The enzyme belongs to the 2-oxoglutarate-dependent-dioxygenases (2-ODD) superfamily. We characterized the FLS gene family of Brassica napus that covers 13 genes, based on the genome sequence of the B. napus cultivar Express 617. The goal was to unravel which BnaFLS genes are relevant for seed flavonol accumulation in the amphidiploid species B. napus. Two BnaFLS1 homoelogs were identified and shown to encode bifunctional enzymes. Both exhibit FLS activity as well as flavanone 3 hydroxylase (F3H) activity, which was demonstrated in vivo and in planta. BnaFLS1-1 and -2 are capable of converting flavanones into dihydroflavonols and further into flavonols. Analysis of spatio temporal transcription patterns revealed similar expression profiles of BnaFLS1 genes. Both are mainly expressed in reproductive organs and co expressed with the genes encoding early steps of flavonoid biosynthesis. Our results provide novel insights into flavonol biosynthesis in B. napus and contribute information for breeding targets with the aim to modify the flavonol content in rapeseed.

scholarly journals Differential expression of the ras gene family in mice.

1987 ◽  
Vol 7 (4) ◽  
pp. 1535-1540 ◽  
Author(s):  
J Leon ◽  
I Guerrero ◽  
A Pellicer
Keyword(s):  
Gene Family ◽  
Differential Expression ◽  
Adult Mouse ◽  
Expression Patterns ◽  
Cellular Functions ◽  
Ras Gene ◽  
Ras Genes ◽  
Mouse Tissues

We compared the expression of the ras gene family (H-ras, K-ras, and N-ras) in adult mouse tissues and during development. We found substantial variations in expression among different organs and in the amounts of the different transcripts originating from each gene, especially for the N-ras gene. The expression patterns were consistent with the reported preferential tissue activation of ras genes and suggested different cellular functions for each of the ras genes.

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