Post-transcriptional Regulation of Rat CYP2E1 Expression: Role of CYP2E1 mRNA Untranslated Regions in Control of Translational Efficiency and Message Stability

2000 ◽  
Vol 376 (1) ◽  
pp. 180-190 ◽  
Author(s):  
Thomas A. Kocarek ◽  
Richard C. Zangar ◽  
Raymond F. Novak
2020 ◽  
Author(s):  
Elise Clayer ◽  
Destiny Dalseno ◽  
Andrew Kueh ◽  
Derek Lacey ◽  
Minhsuang Tsai ◽  
...  

AbstractPost-transcriptional regulation mechanisms regulate mRNA stability or translational efficiency via ribosomes and recent evidence indicates that it is a major determinant of the accurate levels of cytokine mRNAs. While transcriptional regulation of Tnf has been well studied and found to be important for the rapid induction of Tnf mRNA and regulation of the acute phase of inflammation, study of its post-transcriptional regulation has been largely limited to the role of the AU-rich element (ARE), and to a lesser extent, that of the constitutive decay element (CDE). We have identified a new regulatory element (NRE) in the 3’ untranslated region (3’UTR) of Tnf, and demonstrate that ARE, CDE and NRE cooperate to efficiently down regulate Tnf expression and prevent autoimmune inflammatory diseases. We also show for the first time that excessive TNF may lead to embryonic death.


2019 ◽  
Vol 166 (5) ◽  
pp. 375-382 ◽  
Author(s):  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Hiroshi Asahara

Abstract In human genome, there are approximately 1,500 RNA-binding proteins (RBPs). They can regulate mRNA stability or translational efficiency via ribosomes and these processes are known as ‘post-transcriptional regulation’. Accumulating evidences indicate that post-transcriptional regulation is the determinant of the accurate levels of cytokines mRNAs. While transcriptional regulation of cytokines mRNAs has been well studied and found to be important for the rapid induction of mRNA and regulation of the acute phase of inflammation, post-transcriptional regulation by RBPs is essential for resolving inflammation in the later phase, and their dysfunction may lead to severe autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus. For post-transcriptional regulation, RBPs recognize and directly bind to cis-regulatory elements in 3′ untranslated region of mRNAs such as AU-rich or constitutive decay elements and play various roles. In this review, we summarize the recent findings regarding the role of RBPs in the regulation of inflammation.


Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 466
Author(s):  
Marie-Christine Carpentier ◽  
Cécile Bousquet-Antonelli ◽  
Rémy Merret

The recent development of high-throughput technologies based on RNA sequencing has allowed a better description of the role of post-transcriptional regulation in gene expression. In particular, the development of degradome approaches based on the capture of 5′monophosphate decay intermediates allows the discovery of a new decay pathway called co-translational mRNA decay. Thanks to these approaches, ribosome dynamics could now be revealed by analysis of 5′P reads accumulation. However, library preparation could be difficult to set-up for non-specialists. Here, we present a fast and efficient 5′P degradome library preparation for Arabidopsis samples. Our protocol was designed without commercial kit and gel purification and can be easily done in one working day. We demonstrated the robustness and the reproducibility of our protocol. Finally, we present the bioinformatic reads-outs necessary to assess library quality control.


1998 ◽  
Vol 80 (4) ◽  
pp. 307-321
Author(s):  
John E. Hesketh ◽  
M. Helena Vasconcelos ◽  
Giovanna Bermano

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.


1995 ◽  
Vol 305 (2) ◽  
pp. 451-458 ◽  
Author(s):  
L Parry ◽  
R Balaña Fouce ◽  
A E Pegg

Spermidine/spermine N1-acetyltransferase (SSAT) is the rate-limiting enzyme for the degradation and excretion of polyamines in mammalian cells, and its activity is known to be increased enormously on exposure to polyamines and polyamine analogues. The mechanism by which such an analogue, BESM [N1N12-bis(ethyl)spermine], increases the content of SSAT was investigated by transfecting COS-7 cells with plasmids containing SSAT cDNA in the pEUK expression vector. Despite a large increase in mRNA production, there was only a very small increase in SSAT activity in the transfected cells. When BESM was added at 36 h after transfection, there was a large and very rapid increase in SSAT protein amounting to 380-fold in 12 h without any increase in the mRNA. SSAT protein turned over very rapidly, with a half-life of about 20 min. In the presence of BESM, this turnover was greatly reduced, and the half-life increased to more than 13 h. However, this increase was not sufficient to account for all of the increase in SSAT protein, suggesting that there is also regulation of the translation of the mRNA by BESM. Further evidence for such translation regulation was obtained by studying the polysomal distribution of the SSAT mRNA. In the absence of BESM, most of the mRNA was present in fractions which sedimented more slowly than the monoribosome peak. In BESM-treated cells, a significant proportion of the SSAT mRNA was moved into the small-polysome region of the gradient. The expression of SSAT and the effects of BESM on the polysomal distribution of SSAT mRNA were not affected by the 5′- or 3′-untranslated regions of the mRNA, since constructs which lacked all of these regions gave similar results to constructs containing the entire mRNA sequence. These results show that the increased transcription of the SSAT gene that occurs in the presence of polyamine analogues such as BESM is not sufficient for SSAT expression and that post-transcriptional regulation is critical for the control of SSAT content.


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