Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mRNA stability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources
PubMed1999

Cx32 mRNA in rat liver: effects of inflammation on poly(A) tail distribution and mRNA degradation.

Previous studies showed that the expression of connexin 32 (Cx32), the polypeptide subunit component of the major hepatic gap junction, is reduced in liver by changes in mRNA stability during bacterial lipopolysaccharide (LPS)-induced inflammation. In this study, we examined the distribution of Cx32 mRNA poly(A) tail lengths during LPS-induced inflammation, because this is considered the first step in the degradation of many mRNAs. During LPS treatment the first detectable change in Cx32 mRNA was a gradual shortening of its poly(A) tail, which reached a final size of approximately 20 nucleotides. However, the poly(A) tail did not disappear entirely before the bulk of Cx32 mRNA was degraded. Treatment with actinomycin D, which blocks the degradation of Cx32 mRNA after LPS administration, resulted in the appearance of a completely deadenylated mRNA, which otherwise could not be detected. On the contrary, treatment with cycloheximide resulted in a decrease in the stability of Cx32 mRNA without an apparent change of the poly(A) tail size. The effect of cycloheximide on Cx32 mRNA stability seems to be due indirectly to the induction of an inflammatory response by this drug. These results suggest that, similar for many mRNAs, shortening of the poly(A) tail is one of the first steps in the degradation of Cx32 mRNA during inflammation.

Amino Acid Sequence↗
PubMed2000

Regulation of cold shock-induced RNA helicase gene expression in the Cyanobacterium anabaena sp. strain PCC 7120.

Expression of the Anabaena sp. strain PCC 7120 RNA helicase gene crhC is induced by cold shock. crhC transcripts are not detectable at 30 degrees C but accumulate at 20 degrees C, and levels remain elevated for the duration of the cold stress. Light-derived metabolic capability, and not light per se, is required for crhC transcript accumulation. Enhanced crhC mRNA stability contributes significantly to the accumulation of crhC transcripts, with the crhC half-life increasing sixfold at 20 degrees C. The accumulation is reversible, with the cells responding more rapidly to temperature downshifts than to upshifts, as a result of the lack of active mRNA destabilization and the continuation of crhC transcription, at least transiently, after a temperature upshift. Translational inhibitors do not induce crhC expression to cold shock levels, indicating that inhibition of translation is only one of the signals required to activate the cold shock response in Anabaena. Limited amounts of protein synthesis are required for the cold shock-induced accumulation of crhC transcripts, as normal levels of accumulation occur in the presence of tetracycline but are abolished by chloramphenicol. Regulation of crhC expression may also extend to the translational level, as CrhC protein levels do not correlate completely with the pattern of mRNA transcript accumulation. Our experiments indicate that the regulation of crhC transcript accumulation is tightly controlled by both temperature and metabolic activity at the levels of transcription, mRNA stabilization, and translation.

Anabaena↗
PubMed2000

Post-transcriptional regulation of mouse kappa-opioid receptor expression.

Three mRNA variants are generated from the mouse kappa-opioid receptor (KOR) gene. The expression patterns of these KOR mRNA variants in adult animal tissues and during developmental stages are examined. Furthermore, the biological significance of generating these variants is demonstrated with respect to two post-transcriptional mechanisms, i.e., mRNA stability and translation efficiency. Variants A and B are both transcribed from promoter 1 of the KOR gene and expressed from early developmental stages through adult life. Although their sequences differ only at a 30-nucleotide insertion for variant B, these two variants are distinct with regard to their expression patterns, mRNA stability, and translation efficiency. Variant A is expressed ubiquitously in all the tissues examined and has a longer t(1/2) (12 h), whereas variant B is more specific to the central nervous system both pre- and postnatally and has a t(1/2) of approximately 8 h. Variant C is transcribed from promoter 2 of the KOR gene and is most specifically expressed, being detected only in the brain stem, spinal cord, and thalamic/hypothalamic areas of postnatal animals. With regard to protein translation, variants B and C are significantly more efficient than variant A. This study provides the evidence for multiple levels of KOR regulation. The biological implication of the generation of KOR mRNA variants is discussed.

Animals↗
PubMed2005

Altered apolipoprotein A-V expression during the acute phase response is independent of plasma triglyceride levels in mice and humans.

Plasma triglyceride (TG) levels are altered during the acute phase response (APR). Plasma levels of the recently discovered apolipoprotein A-V (apoA-V) are inversely associated with plasma TG. The aim of this study was to investigate the change of apoA-V plasma levels and hepatic apoA-V expression during the APR in relation to plasma TG. During human APR plasma apoA-V was decreased as were plasma TG (each P<0.01). Also early in the course of the murine APR plasma apoA-V levels and hepatic apoA-V expression were decreased and changed in the same direction as plasma TG. Treatment of HepG2 cells with TNF-alpha and IL-1beta decreased apoA-V mRNA levels early by 42% and 55%, respectively (each P<0.001). However, in promoter/reporter assays the human apoA-V promoter was unresponsive to proinflammatory cytokines. Instead, we demonstrate that a significant decrease in apoA-V mRNA stability in response to treatment with TNF-alpha and IL-1beta is the underlying basis of decreased apoA-V expression during the APR (P<0.05). These data demonstrate that (i) apoA-V expression decreases early during the APR due to changes in mRNA stability, and (ii) during the APR apoA-V is not inversely related to plasma TG levels in mice and humans, thereby identifying a relevant pathophysiological setting, in which the previously reported close inverse association between these parameters does not hold true.

Acute-Phase Reaction↗
PubMed2004

Cutting edge: CD28-mediated transcriptional and posttranscriptional regulation of IL-2 expression are controlled through different signaling pathways.

Despite the clear functional importance of CD28 costimulation, the signaling pathways transduced through CD28 have remained controversial. PI3K was identified early as a candidate for CD28 signaling, but conflicting data during the past decade has left the role of PI3K unresolved. In this report, we have resolved this controversy. We show that mutation of the PI3K interaction site in the cytosolic tail of CD28 site disrupts the ability of CD28 to recruit protein kinase C-theta; to the central supramolecular activation cluster (c-SMAC) region of the immunological synapse, promote NF-kappaB nuclear translocation, and enhance IL-2 gene transcription. In contrast, mutation of the PI3K interaction site had no effect on the ability of CD28 to enhance IL-2 mRNA stability. These results suggest that two distinct pathways mediate CD28-induced up-regulation of IL-2 expression, a PI3K-dependent pathway that may function through the immunological synapse to enhance IL-2 transcription and a PI3K-independent pathway that induces IL-2 mRNA stability.

Active Transport, Cell Nucleus↗
PubMed1991

Heme regulates hepatic 5-aminolevulinate synthase mRNA expression by decreasing mRNA half-life and not by altering its rate of transcription.

Hepatic 5-aminolevulinate (ALA) synthase, the first and rate-limiting enzyme in the heme biosynthetic pathway, is known to be feedback repressed by the end product of the pathway, heme. We investigated whether heme regulates ALA synthase mRNA expression transcriptionally or post-transcriptionally in primary cultures of chick embryo hepatocytes. 2-Propyl-2-isopropylacetamide increased the rate of transcription of the ALA synthase gene, whereas heme or an inhibitor of heme biosynthesis, desferrioximine, had no effect on the drug-induced transcription rate. Heme decreased the half-life of ALA synthase mRNA from approximately 3.5 h to 1.2 as recently reported by Drew and Ades (1989, Biochem. Biophys. Res. Commun. 162, 102-107). We also found that the heme-mediated decrease in mRNA stability was prevented by cycloheximide treatment, suggesting that the heme effect was mediated by a labile protein. These results support a model for hepatic ALA synthase regulation in which inducing drugs directly stimulate ALA synthase gene transcription, whereas heme regulates ALA synthase expression post-transcriptionally by modulating mRNA stability as well as by blocking translocation of ALA synthase enzyme into the mitochondrion.

5-Aminolevulinate Synthetase↗
PubMed1995

Differential expression and regulation of hsp70 and hsp90 by phorbol esters and heat shock.

Human peripheral blood monocytes (PBM) produce superoxide anions (O2-.) by a process involving electron transfer from NADPH to O2, catalyzed by the respiratory burst enzyme NADPH oxidase. We have previously shown that phagocytosis, while activating NADPH oxidase, induced in PBM the synthesis of heat shock (HS) proteins (HSP). The present study was undertaken to establish whether this increase in HSP expression was related to O2-. and/or to classical second messengers such as protein kinase C (PKC). Thus, the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) were compared with those of heat shock on the expression, in PBM, of the major HSP, hsp70 and hsp90, using biometabolic labeling, Western and Northern blotting, and gel mobility shift assays. PMA induced the accumulation of mRNA and an increased expression of hsp90 and, to a lesser extent, hsp/hsc70 (hsc is the cognate, constitutive form). This induction was also observed in PBM from patients with chronic granulomatous disease, a genetic defect in NADPH oxidase, and was abolished by the PKC inhibitors staurosporine and H-7. PMA did not cause activation of the HS factor, and the PMA-induced overexpression expression of HSP was not blocked by the transcriptional inhibitor actinomycin D. HSP-specific mRNA stability was increased after PMA exposure as compared with heat shock. These results suggest that O2-. is not involved in the PMA-mediated induction of hsp70 and hsp90 and that, in contrast to HS, PMA increases the expression of HSP as a result of PKC-induced mRNA stabilization rather than of transcriptional activation of HS genes.

Base Sequence↗
PubMed2005

Identification of mechanisms underlying transporter associated with antigen processing deficiency in metastatic murine carcinomas.

Expression of transporter associated with antigen processing (TAP) is often lost in metastatic carcinomas, resulting in defective antigen processing and presentation and escape of the cancer cells from immune surveillance. In this study, the nature of TAP deficiencies in tumors was investigated. By chromatin immunoprecipitation assay, we showed that the recruitment of RNA polymerase II to the TAP-1 gene was impaired in TAP-deficient cells derived from murine melanoma, prostate, and lung carcinomas, compared with TAP-expressing fibroblasts and lymphoma cells. This suggested that the deficiency in TAP-1 expression resulted, at least partially, from a relatively low level of transcription of the TAP-1 gene. Furthermore, levels of TAP-1 promoter activity, as assessed by stable transfections with a reporter construct containing the TAP-1 promoter, were relatively low in TAP-deficient cells. To examine genetic heritability of regulators of TAP-1 promoter activity, TAP- and MHC class I-deficient cells of H-2b origin were fused with wild-type fibroblasts of H-2k origin. Fusion with TAP-expressing cells complemented the low levels of TAP-1 promoter activity in TAP-deficient cells. However, these fused cells exhibited lower levels of TAP-1 mRNA and H-2k than unfused fibroblasts. Further analysis showed that TAP-1 mRNA stability was lower in fused carcinoma fibroblasts than in unfused fibroblasts. Based on these results, we propose that TAP deficiency in many carcinomas is caused by a decrease in activity/expression of trans-acting factors regulating TAP-1 promoter activity, as well as a decrease in TAP-1 mRNA stability. These results have significant implications for understanding immune evasion mechanisms in tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Messenger RNAs in dendrites: localization, stability, and implications for neuronal function.

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several dendritic mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function.

Animals↗
PubMed1996

Trans-synaptic control of NGFI-A and jun-B expression: contrasting transcriptional and post-transcriptional mechanisms directed by common receptors.

Previous studies have demonstrated that of the multiple primary response gene products which are induced in the rat pineal gland through a nocturnally activated adrenoceptor-linked mechanism. JunB is the principal component of a dark phase-specific activator protein-1 DNA binding complex. JunB is therefore implicated as a nuclear component of the mechanisms that determine nocturnal changes in pineal function. It is now shown that the marked increase in jun-B mRNA expression following norepinephrine stimulation in vitro, is mediated through a post-transcriptional mechanism that involves mRNA stabilization. This mode of regulation is contrasted with that controlling the expression of other primary response genes. In the case of NGFI-A, a co-regulated primary response gene which is controlled through a pharmacologically similar pathway, nuclear run-on transcription assays have shown that pineal mRNA levels are elevated through an increase in transcription rate that can be measured both in vitro and in vivo. These results show that multiple molecular mechanisms are engaged to effect the genomic consequences of adrenoceptor stimulation, and that rhythmic changes in gene expression may be controlled by post-transcriptional mechanisms involving mRNA stability.

Adrenergic Agents↗
PubMed2002

Transferrin receptor gene expression and transferrin-bound iron uptake are increased during postischemic rat liver reperfusion.

Iron-catalyzed production of reactive oxygen species is a cause of liver injury after ischemia/reperfusion (I/R). The aim of the present study was to address the regulation of transferrin receptor (TfR), which mediates cellular iron uptake, during I/R. The molecular mechanisms controlling TfR gene expression in vivo during I/R of rat liver were investigated by molecular biology procedures. We also analyzed transferrin-bound iron uptake into surviving liver slices. Increased amounts of TfR protein and messenger RNA (mRNA) were found 2 to 6 hours after reestablishment of blood supply. RNA bandshift analysis showed that iron regulatory protein (IRP) activity was decreased in the first hours of reperfusion, thus indicating that IRP-mediated mRNA stabilization was not involved in early TfR upregulation. On the contrary, increased transcription of the TfR gene in isolated nuclei was observed during reperfusion; during the ischemic phase this was preceded by enhanced binding of hypoxia inducible factor (HIF-1) to a DNA sequence derived from the TfR promoter. TfR2 mRNA levels were also enhanced after reperfusion. The increased expression of TfR at the cell surface resulted in increased uptake of transferrin-bound-iron into surviving liver slices; however, iron was not incorporated into ferritin. In conclusion, HIF-1 mediated activation of TfR gene transcription and IRP-mediated increase of TfR mRNA stability ensure a steady induction of TfR, and hence higher iron uptake in reperfused rat liver. TfR-mediated entry of the metal into liver cells may represent a source of catalytically active iron, which may play a role in reperfusion damage.

Animals↗
PubMed2002

Leustroducsin B activates nuclear factor-kappaB via the acidic sphingomyelinase pathway in human bone marrow-derived stromal cell line KM-102.

The novel colony-stimulating factor (CSF) inducer leustroducsin B (LSN-B), which was isolated from Streptomyces platensis, has been shown to have potent cytokine-inducing activities in clonal human bone marrow-derived stromal cell line KM-102 and in primary human bone marrow-derived stromal cells. In this study, we investigated the signal transduction pathway of LSN-B using luciferase expression plasmids linked to the 5'-flanking region of interleukin-8 (IL-8) and that of the IL-11 gene. In KM-102 cells, LSN-B induced luciferase activity both in the wild-type and in the activated protein 1 (AP-1) site point-mutated IL-8 promoter. The mutation in the nuclear factor-kappaB (NF-kappaB) site abrogated LSN-B-stimulated induction of the reporter gene. LSN-B-inducing activity was inhibited by (1) N-acetyl-L-cysteine, a well-characterized antioxidant, (2) cationic amphiphilic drugs, inhibitors of acidic sphingomyelinase (A-SMase), and (3) D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). These observations suggest that LSN-B potentiates the A-SMase-mediated signaling pathway to stimulate NF-kappaB. In contrast, LSN-B did not induce IL-11 promoter-driven luciferase activity. The observed increase in IL-11 mRNA stability by LSN-B indicates that the inducible production of IL-11 by LSN-B is regulated at the posttranscriptional level. In addition, inhibition of LSN-B-mediated induction of IL-11 production by cationic amphiphilic drugs and D609 in KM-102 cells demonstrates that increased IL-11 mRNA stability by LSN-B might be mediated via NF-kappaB activation. From these results, we suggest that LSN-B induces cytokine production through at least two separate mechanisms, at the transcriptional level and at the posttranscriptional level via NF-kappaB activation.

Acetylcysteine↗
PubMed2006

Endotoxin induces toll-like receptor 4 expression in vascular smooth muscle cells via NADPH oxidase activation and mitogen-activated protein kinase signaling pathways.

OBJECTIVE: Toll-like receptor 4 (TLR4) plays a major role mediating endotoxin-induced cellular inflammation and regulates vascular smooth muscle cell (VSMC) proliferation, which is related to atherogenesis and restenosis. This study was conducted to investigate the mechanisms involved in lipopolysaccharide (LPS)-induced TLR4 expression in VSMCs. METHODS AND RESULTS: Stimulation of human aortic smooth muscle cells (HASMCs) with LPS significantly increased TLR4 expression. The increase was regulated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (including the activation of subunits p47(phox) and Rac1), which mediates the production of reactive oxygen species and the activation of intracellular mitogen-activated protein kinase signaling pathways. Treatment with polyethylene-glycol-conjugated superoxide dismutase, N-acetylcysteine (NAC), diphenylene iodonium (DPI), or apocynin significantly decreased LPS-induced TLR4 expression. An actinomycin D chase experiment showed that LPS increased the half-life of TLR4 mRNA. Inhibition of NADPH oxidase activity by DPI, apocynin, or NAC significantly decreased TLR4 mRNA stability, as did the knock-down of RAC1 gene expression by RNA interference. We also demonstrated in an animal model that LPS administration led to a significant elevation of balloon-injury-induced neointimal hyperplasia, and of TLR4 expression, in rabbit aorta. CONCLUSIONS: These findings suggest that NADPH oxidase activation, mRNA stabilization, and MAPK signaling pathways play critical roles in LPS-enhanced TLR4 expression in HASMCs, which contributes to vascular inflammation and cardiovascular disorders.

Acetophenones↗
PubMed1996

Transcriptional and post-transcriptional regulation of interleukin-8.

Steady-state mRNA for interleukin (IL) 8 persists significantly longer than mRNA for tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS) stimulated human whole blood. Nuclear run-ons demonstrated consistent levels of transcriptional activity of the IL-8 gene at 2 and 26 hours after LPS stimulation when compared with the rapid induction and arrest of the TNF-alpha gene. Inhibition of cellular transcription with actinomycin D added at 2 hours after LPS resulted in the substantial decrease of both IL-8 and TNF-alpha mRNAs, demonstrating half-lives of 4.6 and 2.3 hours, respectively. In contrast, inhibition of transcription at 23 hours after LPS revealed extremely stable IL-8 mRNA with a half-life of > 10 hours. The half-life of beta-actin in the same actinomycin-D-treated samples did not vary significantly from the half-life calculated at the 2-hour time point (5.5 hours versus 5.6 hours), indicating that the observed IL-8 mRNA stability was not an artifact of the system. Both IL-8 and TNF-alpha protein levels decreased when actinomycin D was added 2 hours after LPS stimulation. However, no effect in IL-8 protein levels was evident when actinomycin D was added at 23 hours after LPS. These results demonstrate that IL-8 mRNA stability is controlled at both the transcriptional and posttranscriptional levels of gene regulation.

Humans↗
PubMed2006

Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis.

Terminal erythropoiesis is accompanied by extreme demand for iron to ensure proper hemoglobinization. Thus, erythroblasts must modify the "standard" post-transcriptional feedback regulation, balancing expression of ferritin (Fer; iron storage) versus transferrin receptor (TfR1; iron uptake) via specific mRNA binding of iron regulatory proteins (IRPs). Although erythroid differentiation involves high levels of incoming iron, TfR1 mRNA stability must be sustained and Fer mRNA translation must not be activated because iron storage would counteract hemoglobinization. Furthermore, translation of the erythroid-specific form of aminolevulinic acid synthase (ALAS-E) mRNA, catalyzing the first step of heme biosynthesis and regulated similarly as Fer mRNA by IRPs, must be ensured. We addressed these questions using mass cultures of primary murine erythroid progenitors from fetal liver, either undergoing sustained proliferation or highly synchronous differentiation. We indeed observed strong inhibition of Fer mRNA translation and efficient ALAS-E mRNA translation in differentiating erythroblasts. Moreover, in contrast to self-renewing cells, TfR1 stability and IRP mRNA binding were no longer modulated by iron supply. These and additional data stemming from inhibition of heme synthesis with succinylacetone or from iron overload suggest that highly efficient utilization of iron in mitochondrial heme synthesis during normal erythropoiesis alters the regulation of iron metabolism via the IRE/IRP system.

Animals↗
PubMed1991

Recombinant interferon-gamma differently affects DQA and DRA gene expression in two human melanoma clones: transcriptional and posttranscriptional regulation.

In a previous study, two human melanoma HLA class-II-negative clones have been shown to respond differently to recombinant interferon gamma (rINF-gamma). In fact, in clone 9229/18, rINF-gamma treatment led to a coordinate expression of both DR and DQ genes, whereas in clone 9229/5, a high increase in steady-state mRNA levels and cell surface antigen expression could be observed for DR but not for DQ genes. The molecular mechanism underlying such a different behavior was investigated and DQA gene regulation was studied both at the transcriptional and posttranscriptional level. Nuclear run-on experiments were performed on 9229/5 and 9229/18 clones. Treatment with rINF-gamma at 1,000 U/ml for 24 h led to a coordinate transcriptional activation of DRA and DQA genes in 9229/18 clone, whereas in clone 9229/5 it strongly augmented the rate of transcription of DRA but not DQA genes. For all class II genes studied, both melanoma clones showed a basal rate of transcription that never led to a mature cytoplasmatic mRNA. To study whether posttranscriptional mechanisms could affect DQA mRNA stability, a comparison was performed between mRNA turnover in 9229/18 cells treated with actinomycin D and actinomycin D plus cyclohexamide following rINF-gamma treatment. In the absence of protein synthesis, the t1/2 of specific DQA mRNA was largely reduced, showing that a short-lived protein is required to stabilize human DQA mRNA in melanoma cells. Our results indicate that DQA gene is subjected to a tight regulation, acting both at the transcriptional and posttranscriptional levels and that DQA and DRA genes can be differentially regulated at the transcriptional level by rINF-gamma in a melanoma clone such as 9229/5.

Base Sequence↗
PubMed2001

BSF binds specifically to the bicoid mRNA 3' untranslated region and contributes to stabilization of bicoid mRNA.

The early stages of Drosophila melanogaster development rely extensively on posttranscriptional forms of gene regulation. Deployment of the anterior body patterning morphogen, the Bicoid protein, requires both localization and translational regulation of the maternal bicoid mRNA. Here we provide evidence that the bicoid mRNA is also selectively stabilized during oogenesis. We identify and isolate a protein, BSF, that binds specifically to IV/V RNA, a minimal form of the bicoid mRNA 3' untranslated region that supports a normal program of mRNA localization during oogenesis. Mutations that disrupt the BSF binding site in IV/V RNA or substantially reduce the level of BSF protein lead to reduction in IV/V RNA levels, indicating a role for BSF in RNA stabilization. The BSF protein is novel and lacks all of the characterized RNA binding motifs. However, BSF does include multiple copies of the PPR motif, whose function is unknown but appears in other proteins with roles in RNA metabolism.

Amino Acid Sequence↗
PubMed2004

Codon-optimized genes that enable increased heterologous expression in mammalian cells and elicit efficient immune responses in mice after vaccination of naked DNA.

Many of the problems related with mammalian gene expression, such as low translation efficiency and mRNA halflife, can be solved by means of a rational gene design, based on modern bioinformatics, followed by the de novo generation of a synthetic gene. Moreover, high expression rates and prolonged mRNA stability are not only crucial for heterologous mammalian expression, but, in particular, are important for the generation of effective DNA vaccines. In this chapter we show that an optimized synthetic gene encoding the HIV-1 Pr55gag outperforms wild-type gene driven expression by several orders of magnitude. RNA analysis revealed that this positive effect was mostly due to increased mRNA stability of the optimized transcripts. Moreover, mice vaccinated with the optimized gag gene elicited a much stronger immune response against Pr55gag than the control groups immunized with the respective wild-type gene.

Animals↗