Genes

2019 ◽  
pp. 162-185
Keyword(s):  
Environmental Factors ◽  
Messenger Rna ◽  
Point Mutations ◽  
Mrna Translation ◽  
Dna Bases ◽  
Small Scale ◽  
Genetic Mutations ◽  
Base Pairs ◽  
Frameshift Mutations ◽  
Specific Proteins

Genes are regions on DNA that contain the instructions for making specific proteins. In humans, genes vary in size from hundreds of DNA bases to over 3 million base pairs. From DNA to proteins, two steps are involved. Transcription is accessing the gene and reading the instructions therein in the nucleus producing as a single strand of RNA called messenger RNA (mRNA). Translation is reading the instructions on mRNA to assemble the specified proteins on the surface of ribosomes. Genetic mutations are heritable, small-scale alterations in one or more base pairs that damage DNA. Although new mutations introduce new variation, these are constantly removed from populations. Mutations can arise naturally during DNA replication or can be caused by environmental factors like chemicals or radiation. They can be harmful, neutral, or beneficial to the organism and are generally of five types: point mutations, frameshift mutations, transposons, transitions, and transversions. This chapter explores this aspect of genes.

scholarly journals Protein synthesis in the dendrite

2002 ◽  
Vol 357 (1420) ◽  
pp. 521-529 ◽  
Author(s):  
Shao Jun Tang ◽  
Erin M. Schuman
Keyword(s):  
Protein Synthesis ◽  
Neural Plasticity ◽  
Messenger Rna ◽  
Mrna Translation ◽  
Synaptic Activity ◽  
Synaptic Proteins ◽  
Local Source ◽  
Synaptic Protein ◽  
Specific Proteins ◽  
Molecular Nature

In neurons, many proteins that are involved in the transduction of synaptic activity and the expression of neural plasticity are specifically localized at synapses. How these proteins are targeted is not clearly understood. One mechanism is synaptic protein synthesis. According to this idea, messenger RNA (mRNA) translation from the polyribosomes that are observed at the synaptic regions provides a local source of synaptic proteins. Although an increasing number of mRNA species has been detected in the dendrite, information about the synaptic synthesis of specific proteins in a physiological context is still limited. The physiological function of synaptic synthesis of specific proteins in synaptogenesis and neural plasticity expression remains to be shown. Experiments aimed at understanding the mechanisms and functions f synaptic protein synthesis might provide important information about the molecular nature of neural plasticity.

Translational pathophysiology: a novel molecular mechanism of human disease

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3280-3288 ◽  
Author(s):  
Mario Cazzola ◽  
Radek C. Skoda
Keyword(s):  
Human Disease ◽  
Messenger Rna ◽  
Rna Binding ◽  
Kinase Inhibitor ◽  
Rna Binding Proteins ◽  
Point Mutations ◽  
Ribosomal Subunit ◽  
Mrna Translation ◽  
Start Codon ◽  
Stem Loop

Abstract In higher eukaryotes, the expression of about 1 gene in 10 is strongly regulated at the level of messenger RNA (mRNA) translation into protein. Negative regulatory effects are often mediated by the 5′-untranslated region (5′-UTR) and rely on the fact that the 40S ribosomal subunit first binds to the cap structure at the 5′-end of mRNA and then scans for the first AUG codon. Self-complementary sequences can form stable stem-loop structures that interfere with the assembly of the preinitiation complex and/or ribosomal scanning. These stem loops can be further stabilized by the interaction with RNA-binding proteins, as in the case of ferritin. The presence of AUG codons located upstream of the physiological start site can inhibit translation by causing premature initiation and thereby preventing the ribosome from reaching the physiological start codon, as in the case of thrombopoietin (TPO). Recently, mutations that cause disease through increased or decreased efficiency of mRNA translation have been discovered, defining translational pathophysiology as a novel mechanism of human disease. Hereditary hyperferritinemia/cataract syndrome arises from various point mutations or deletions within a protein-binding sequence in the 5′-UTR of the L-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinemia and severity of cataract in affected individuals. Hereditary thrombocythemia (sometimes called familial essential thrombocythemia or familial thrombocytosis) can be caused by mutations in upstream AUG codons in the 5′-UTR of the TPO mRNA that normally function as translational repressors. Their inactivation leads to excessive production of TPO and elevated platelet counts. Finally, predisposition to melanoma may originate from mutations that create translational repressors in the 5′-UTR of the cyclin-dependent kinase inhibitor–2A gene.

Translational pathophysiology: a novel molecular mechanism of human disease

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3280-3288 ◽  
Author(s):  
Mario Cazzola ◽  
Radek C. Skoda
Keyword(s):  
Human Disease ◽  
Messenger Rna ◽  
Rna Binding ◽  
Kinase Inhibitor ◽  
Rna Binding Proteins ◽  
Point Mutations ◽  
Ribosomal Subunit ◽  
Mrna Translation ◽  
Start Codon ◽  
Stem Loop

In higher eukaryotes, the expression of about 1 gene in 10 is strongly regulated at the level of messenger RNA (mRNA) translation into protein. Negative regulatory effects are often mediated by the 5′-untranslated region (5′-UTR) and rely on the fact that the 40S ribosomal subunit first binds to the cap structure at the 5′-end of mRNA and then scans for the first AUG codon. Self-complementary sequences can form stable stem-loop structures that interfere with the assembly of the preinitiation complex and/or ribosomal scanning. These stem loops can be further stabilized by the interaction with RNA-binding proteins, as in the case of ferritin. The presence of AUG codons located upstream of the physiological start site can inhibit translation by causing premature initiation and thereby preventing the ribosome from reaching the physiological start codon, as in the case of thrombopoietin (TPO). Recently, mutations that cause disease through increased or decreased efficiency of mRNA translation have been discovered, defining translational pathophysiology as a novel mechanism of human disease. Hereditary hyperferritinemia/cataract syndrome arises from various point mutations or deletions within a protein-binding sequence in the 5′-UTR of the L-ferritin mRNA. Each unique mutation confers a characteristic degree of hyperferritinemia and severity of cataract in affected individuals. Hereditary thrombocythemia (sometimes called familial essential thrombocythemia or familial thrombocytosis) can be caused by mutations in upstream AUG codons in the 5′-UTR of the TPO mRNA that normally function as translational repressors. Their inactivation leads to excessive production of TPO and elevated platelet counts. Finally, predisposition to melanoma may originate from mutations that create translational repressors in the 5′-UTR of the cyclin-dependent kinase inhibitor–2A gene.

scholarly journals Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Zoltán Kis ◽  
Cleo Kontoravdi ◽  
Robin Shattock ◽  
Nilay Shah
Keyword(s):  
Production Process ◽  
Messenger Rna ◽  
Vaccination Campaign ◽  
Vaccine Dose ◽  
Economic Feasibility ◽  
Small Scale ◽  
Production Scale ◽  
Working Volume ◽  
Global Demand ◽  
The Impact

To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) and one self-amplifying RNA (saRNA) vaccines, all currently under clinical development, as well as for a hypothetical next-generation saRNA vaccine. The impact of key process design and operation uncertainties on the performance of the production process was assessed. The RNA vaccine drug substance (DS) production rates, volumes and costs are mostly impacted by the RNA amount per vaccine dose and to a lesser extent by the scale and titre in the production process. The resources, production scale and speed required to meet global demand vary substantially in function of the RNA amount per dose. For lower dose saRNA vaccines, global demand can be met using a production process at a scale of below 10 L bioreactor working volume. Consequently, these small-scale processes require a low amount of resources to set up and operate. RNA DS production can be faster than fill-to-finish into multidose vials; hence the latter may constitute a bottleneck.

Species Responses to Grazing and Environmental-Factors in an Arid Halophytic Shrubland Community

1987 ◽  
Vol 35 (2) ◽  
pp. 135 ◽  
Author(s):  
RB Hacker
Keyword(s):  
Environmental Factors ◽  
Soil Salinity ◽  
Large Scale ◽  
Chemical Properties ◽  
Grazing Pressure ◽  
Aerial Photographs ◽  
Small Scale ◽  
Factors Affecting ◽  
Species Responses

Species responses to grazing and environmental factors were studied in an arid halophytic shrubland community in Western Australia. The grazing responses of major shrub species were defined by using reciprocal averaging ordination of botanical data, interpreted in conjunction with a similar ordination of soil chemical properties and measures of soil erosion derived from large-scale aerial photographs. An apparent small-scale interaction between grazing and soil salinity was also defined. Long-term grazing pressure is apparently reduced on localised areas of high salinity. Environmental factors affecting species distribution are complex and appear to include soil salinity, soil cationic balance, geomorphological variation and the influence of cryptogamic crusts on seedling establishment.

scholarly journals Bacteriophage P22 Antitermination boxB Sequence Requirements Are Complex and Overlap with Those of λ

2008 ◽  
Vol 190 (12) ◽  
pp. 4263-4271 ◽  
Author(s):  
Alexis I. Cocozaki ◽  
Ingrid R. Ghattas ◽  
Colin A. Smith
Keyword(s):  
Consensus Sequence ◽  
Point Mutations ◽  
Resonance Structure ◽  
Moderate Activity ◽  
Nuclear Magnetic Resonance Structure ◽  
Bacteriophage P22 ◽  
Base Pairs ◽  
Rna Hairpins ◽  
Transcription Antitermination ◽  
Theories Of Evolution

ABSTRACT Transcription antitermination in phages λ and P22 uses N proteins that bind to similar boxB RNA hairpins in regulated transcripts. In contrast to the λ N-boxB interaction, the P22 N-boxB interaction has not been extensively studied. A nuclear magnetic resonance structure of the P22 N peptide boxBleft complex and limited mutagenesis have been reported but do not reveal a consensus sequence for boxB. We have used a plasmid-based antitermination system to screen boxBs with random loops and to test boxB mutants. We find that P22 N requires boxB to have a GNRA-like loop with no simple requirements on the remaining sequences in the loop or stem. U:A or A:U base pairs are strongly preferred adjacent to the loop and appear to modulate N binding in cooperation with the loop and distal stem. A few GNRA-like hexaloops have moderate activity. Some boxB mutants bind P22 and λ N, indicating that the requirements imposed on boxB by P22 N overlap those imposed by λ N. Point mutations can dramatically alter boxB specificity between P22 and λ N. A boxB specific for P22 N can be mutated to λ N specificity by a series of single mutations via a bifunctional intermediate, as predicted by neutral theories of evolution.

scholarly journals Generation of asymmetry during development. Segregation of type-specific proteins in Caulobacter.

1979 ◽  
Vol 81 (1) ◽  
pp. 123-136 ◽  
Author(s):  
N Agabian ◽  
M Evinger ◽  
G Parker
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Messenger Rna ◽  
Cell Types ◽  
Specific Protein ◽  
Soluble Proteins ◽  
Specific Cell ◽  
Daughter Cells ◽  
Specific Proteins ◽  
Entire Cell

An essential event in developmental processes is the introduction of asymmetry into an otherwise undifferentiated cell population. Cell division in Caulobacter is asymmetric; the progeny cells are structurally different and follow different sequences of development, thus providing a useful model system for the study of differentiation. Because the progeny cells are different from one another, there must be a segregation of morphogenetic and informational components at some time in the cell cycle. We have examined the pattern of specific protein segregation between Caulobacter stalked and swarmer daughter cells, with the rationale that such a progeny analysis would identify both structurally and developmentally important proteins. To complement the study, we have also examined the pattern of protein synthesis during synchronous growth and in various cellular fractions. We show here, for the first time, that the association of proteins with a specific cell type may result not only from their periodicity of synthesis, but also from their pattern of distribution at the time of cell division. Several membrane-associated and soluble proteins are segregated asymmetrically between progeny stalked and swarmer cells. The data further show that a subclass of soluble proteins becomes associated with the membrane of the progeny stalked cells. Therefore, although the principal differentiated cell types possess different synthetic capabilities and characteristic proteins, the asymmetry between progeny stalked and swarmer cells is generated primarily by the preferential association of specific soluble proteins with the membrane of only one daughter cell. The majority of the proteins which exhibit this segregation behavior are synthesized during the entire cell cycle and exhibit relatively long, functional messenger RNA half-lives.

scholarly journals DNA SEQUENCES OF FRAMESHIFT AND OTHER MUTATIONS INDUCED BY ICR-170 IN YEAST

Genetics ◽  
1985 ◽  
Vol 111 (2) ◽  
pp. 233-241
Author(s):  
Joachim F Ernst ◽  
D Michael Hampsey ◽  
Fred Sherman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Sequence Analysis ◽  
Genetic Analysis ◽  
Dna Sequences ◽  
Induced Mutations ◽  
Sequence Analyses ◽  
Base Pairs ◽  
Yeast Saccharomyces Cerevisiae ◽  
Frameshift Mutations

ABSTRACT ICR-170-induced mutations in the CYC1 gene of the yeast Saccharomyces cerevisiae were investigated by genetic and DNA sequence analyses. Genetic analysis of 33 cyc1 mutations induced by ICR-170 and sequence analysis of eight representatives demonstrated that over one-third were frameshift mutations that occurred at one site corresponding to amino acid positions 29-30, whereas the remaining mutations were distributed more-or-less randomly, and a few of these were not frameshift mutations. The sequence results indicate that ICR-170 primarily induces G·C additions at sites containing monotonous runs of three G·C base pairs. However, some (see PDF) sites within the CYC1 gene were not mutated by ICR-170. Thus, ICR-170 is a relatively specific mutagen that preferentially acts on certain sites with monotonous runs of G·C base pairs.

scholarly journals Enhancer and promoter elements directing activation and glucocorticoid repression of the alpha 1-fetoprotein gene in hepatocytes.

1988 ◽  
Vol 8 (4) ◽  
pp. 1398-1407 ◽  
Author(s):  
M Guertin ◽  
H LaRue ◽  
D Bernier ◽  
O Wrange ◽  
M Chevrette ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Transient Expression ◽  
Promoter Activity ◽  
Gene Activation ◽  
Point Mutations ◽  
Binding Assays ◽  
Recognition Sequence ◽  
Base Pairs ◽  
Receptor Recognition ◽  
Afp Promoter

Mutations were introduced in 7 kilobases of 5'-flanking rat alpha 1-fetoprotein (AFP) genomic DNA, linked to the chloramphenicol acetyltransferase gene. AFP promoter activity and its repression by a glucocorticoid hormone were assessed by stable and transient expression assays. Stable transfection assays were more sensitive and accurate than transient expression assays in a Morris 7777 rat hepatoma recipient (Hepa7.6), selected for its strong AFP repression by dexamethasone. The segment of DNA encompassing a hepatocyte-constitutive chromatin DNase I-hypersensitive site at -3.7 kilobases and a liver developmental stage-specific site at -2.5 kilobases contains interacting enhancer elements sufficient for high AFP promoter activity in Hepa7.6 or HepG2 cells. Deletions and point mutations define an upstream promoter domain of AFP gene activation, operating with at least three distinct promoter-activating elements, PEI at -65 base pairs, PEII at -120 base pairs, and DE at -160 base pairs. PEI and PEII share homologies with albumin promoter sequences, PEII is a near-consensus nuclear factor I recognition sequence, and DE overlaps a glucocorticoid receptor recognition sequence. An element conferring glucocorticoid repression of AFP gene activity is located in the upstream AFP promoter domain. Receptor-binding assays indicate that this element is the glucocorticoid receptor recognition sequence which overlaps with promoter-activating element DE.

scholarly journals Effect of post-ischaemic recovery on albumin synthesis and relative amount of translatable albumin messenger RNA in rat liver

1982 ◽  
Vol 204 (1) ◽  
pp. 197-202 ◽  
Author(s):  
G Cairo ◽  
L Schiaffonati ◽  
M G Aletti ◽  
A Bernelli-Zazzera
Keyword(s):  
Protein Synthesis ◽  
Total Protein ◽  
Messenger Rna ◽  
Relative Proportion ◽  
Liver Homogenate ◽  
Albumin Synthesis ◽  
Specific Proteins ◽  
Membrane Bound ◽  
Albumin Mrna

In liver cells recovering from reversible ischaemia, total protein synthesis by postmitochondrial supernatant and membrane-bound and free polyribosomes is not different from that in sham-operated controls. However, the relative proportion of specific proteins is changed, since the incorporation of [3H]leucine in vivo into liver albumin, relative to incorporation into total protein, as determined by precipitation of labelled albumin with the specific antibody, decreases by 40-50% in post-ischaemic livers. Cell-free synthesis by membrane-bound polyribosomes and poly(A)-enriched RNA isolated from unfractionated liver homogenate shows that the decrease in albumin synthesis in liver of rats recovering from ischaemia is due to the relative decrease in translatable albumin mRNA.

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