scholarly journals The 3′-untranslated region of the mouse cholesterol 7α-hydroxylase mRNA contains elements responsive to post-transcriptional regulation by bile acids

1997 ◽  
Vol 328 (2) ◽  
pp. 393-399 ◽  
Author(s):  
B. Luis AGELLON ◽  
K. Sukhinder CHEEMA
Keyword(s):  
Transcriptional Regulation ◽  
Bile Acids ◽  
Untranslated Region ◽  
Transgene Expression ◽  
Hepatoma Cells ◽  
Early Gene ◽  
Transcriptional Level ◽  
Acid Uptake ◽  
Post Transcriptional Regulation ◽  
Conjugated Bile Acids

To investigate the importance of the 3ʹ-untranslated region (UTR) of the mouse cholesterol 7α-hydroxylase (cyp7) mRNA in post-transcriptional regulation of expression of the cyp7 gene, chimaeric genes encoding mRNA containing the structural sequence of chloramphenicol acetyltransferase (CAT) linked to either the 3ʹ-UTR of the mouse cyp7 mRNA or the SV40 early gene mRNA were constructed. The human cytomegalovirus (CMV) promoter was used to drive the expression of all the chimaeric genes. Thus the transgenes had identical sequences in the promoter, the regions encoding the 5ʹ-UTR and translated sequence but differed in the region encoding the 3ʹ-UTR of their respective mRNA species. The transgene containing the entire cyp7 3ʹ-UTR (designated CMV.CAT.CYP7) gave rise to CAT activity in transfected hepatoma cells that was one-quarter of that obtained in cells transfected with the transgene containing the SV40 3ʹ-UTR (designated CMV.CAT.SV40). The 3ʹ-UTR of the cyp7 mRNA contains sequences resembling AU-rich elements (AREs). Deleting eight of nine putative AREs from the CYP7 3ʹ-UTR sequence increased the CAT activity to a level greater than that observed for CMV.CAT.SV40, whereas deletion of the intron region had no effect. These results show that the AREs of the 3ʹ-UTR of the cyp7 mRNA decrease transgene expression. Bile acids are known to repress the expression of the cyp7 gene. To test whether the 3ʹ-UTR of the cyp7 mRNA has a role in this process, the expression of the chimaeric genes was evaluated in hepatoma cells competent for bile acid uptake. Conjugated bile acids, but not unconjugated bile acids, further decreased the expression of the CMV.CAT.CYP7 transgene. The same bile acids had no effect on the expression of the CMV.CAT.SV40 transgene. Deletion of the intron from the cyp7 sequence did not alter the CAT activity compared with the parental plasmid, and also did not alter the sensitivity of the transgene to the conjugated bile acids. Deletion of the AREs from the cyp7 3ʹ-UTR, which increased the expression of the transgene, did not abolish the sensitivity of the transgene to repression by conjugated bile acids. Thus the 3ʹ-UTR of the mouse cyp7 mRNA also contains elements that facilitate the further repression of transgene expression in the presence of conjugated bile acids. The results indicate that the 3ʹ-UTR of the mouse cyp7 mRNA contains information specifying regulation at the post-transcriptional level.

Post-transcriptional regulation of Xwnt-8 expression is required for normal myogenesis during vertebrate embryonic development

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3371-3380
Author(s):  
Q. Tian ◽  
T. Nakayama ◽  
M.P. Dixon ◽  
J.L. Christian
Keyword(s):  
Transcriptional Regulation ◽  
Untranslated Region ◽  
Critical Role ◽  
Regulatory Elements ◽  
Rna Degradation ◽  
Transcriptional Level ◽  
Embryonic Patterning ◽  
Sequence Element ◽  
Zygotic Gene ◽  
Post Transcriptional Regulation

The Xenopus Wnt-8 gene is transiently expressed in ventral and lateral mesoderm during gastrulation and plays a critical role in patterning these tissues. In the current study, we show that the spatial and temporal pattern of expression of endogenous Xwnt-8 is regulated, in part, at a post-transcriptional level. We have identified a novel sequence element in the 3′ untranslated region of the Xwnt-8 RNA that controls the polyadenylation status of reporter and endogenous Xwnt-8 RNAs, directs rapid RNA degradation beginning precisely at the early gastrula stage, and represses translation of transcripts throughout development. Expression of endogenous Xwnt-8 is normally downregulated within lateral (presomitic) mesoderm following gastrulation. We demonstrate that rapid degradation of Xwnt-8 transcripts, mediated by these regulatory elements in the 3′ untranslated region, is essential to this process and that downregulation is required to prevent overcommitment of somitic cells to a myogenic fate. These studies demonstrate a role for post-transcriptional regulation of zygotic gene expression in vertebrate embryonic patterning.

Post-transcriptional regulation of ULBP1 ligand for the activating immunoreceptor NKG2D involves 3′ untranslated region

2011 ◽  
Vol 72 (6) ◽  
pp. 470-478 ◽  
Author(s):  
Heike Himmelreich ◽  
Arina Mathys ◽  
Aleksandra Wodnar-Filipowicz ◽  
Christian P. Kalberer
Keyword(s):  
Transcriptional Regulation ◽  
Untranslated Region ◽  
Post Transcriptional Regulation

scholarly journals Bile Acid Uptake Transporters as Targets for Therapy

2017 ◽  
Vol 35 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Davor Slijepcevic ◽  
Stan F.J. van de Graaf
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Energy Homeostasis ◽  
Sodium Taurocholate ◽  
Hepatic Uptake ◽  
Farnesoid X Receptor ◽  
Acid Uptake ◽  
Bile Acid Uptake ◽  
Uptake Transporters ◽  
Conjugated Bile Acids

Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.

scholarly journals Ribosome-Profiling Reveals Restricted Post Transcriptional Expression of Antiviral Cytokines and Transcription Factors during SARS-CoV-2 Infection

2021 ◽  
Vol 22 (7) ◽  
pp. 3392
Author(s):  
Marina R. Alexander ◽  
Aaron M. Brice ◽  
Petrus Jansen van Vuren ◽  
Christina L. Rootes ◽  
Leon Tribolet ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Host Response ◽  
High Viral Load ◽  
Ribosome Profiling ◽  
Epithelial Cell Line ◽  
Transcriptional Level ◽  
Human Lung Epithelial Cell ◽  
Post Transcriptional Regulation ◽  
The Impact

The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here, we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.

scholarly journals Targeting of Post-Transcriptional Regulation as Treatment Strategy in Acute Leukemia

2020 ◽  
Author(s):  
Paulina Podszywalow-Bartnicka ◽  
Magdalena Wolczyk ◽  
Katarzyna Piwocka
Keyword(s):  
Transcriptional Regulation ◽  
Acute Leukemia ◽  
Cancer Cells ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Profile ◽  
Cellular Protein ◽  
Special Focus ◽  
Transcriptional Level ◽  
Post Transcriptional Regulation

Post-transcriptional regulation is an important step of gene expression that allows to fine-tune the cellular protein profile (so called proteome) according to the current demands. That mechanism has been developed to aid survival under stress conditions, however it occurs to be hijacked by cancer cells. Adjustment of the protein profile remodels signaling in cancer cells to adapt to therapeutic treatment, thereby enabling persistence despite unfavorable environment or accumulating mutations. The proteome is shaped at the post-transcriptional level by numerous mechanisms such as alternative splicing, mRNA modifications and triage by RNA binding proteins, change of ribosome composition or signaling, which altogether regulate the translation process. This chapter is an overview of the translation disturbances found in leukemia and their role in development of the disease, with special focus on the possible therapeutic strategies tested in acute leukemia which target elements of those regulatory mechanisms.

scholarly journals Post-transcriptional Regulation of RNase-L Expression Is Mediated by the 3′-Untranslated Region of Its mRNA

2007 ◽  
Vol 282 (11) ◽  
pp. 7950-7960 ◽  
Author(s):  
Xiao-Ling Li ◽  
Jesper B. Andersen ◽  
Heather J. Ezelle ◽  
Gerald M. Wilson ◽  
Bret A. Hassel
Keyword(s):  
Transcriptional Regulation ◽  
Untranslated Region ◽  
Rnase L ◽  
Post Transcriptional Regulation

scholarly journals Ribosome-profiling reveals restricted post transcriptional expression of antiviral cytokines and transcription factors during SARS-CoV-2 infection

2021 ◽  
Author(s):  
Marina R. Alexander ◽  
Aaron M. Brice ◽  
Petrus Jansen van Vuren ◽  
Christina L. Rootes ◽  
Leon Tribolet ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Host Response ◽  
High Viral Load ◽  
Ribosome Profiling ◽  
Epithelial Cell Line ◽  
Transcriptional Level ◽  
Human Lung Epithelial Cell ◽  
Post Transcriptional Regulation ◽  
The Impact

ABSTRACTThe global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.

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