scholarly journals Post-transcriptional regulation of the content of spermidine/spermine N1-acetyltransferase by N1N12-bis(ethyl)spermine

1995 ◽  
Vol 305 (2) ◽  
pp. 451-458 ◽  
Author(s):  
L Parry ◽  
R Balaña Fouce ◽  
A E Pegg
Keyword(s):  
Transcriptional Regulation ◽  
Half Life ◽  
Mammalian Cells ◽  
Significant Proportion ◽  
Untranslated Regions ◽  
Translation Regulation ◽  
Polyamine Analogues ◽  
Post Transcriptional Regulation ◽  
Rate Limiting ◽  
Ssat Activity

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.

Rhythmic post-transcriptional regulation of the circadian clock protein mPER2 in mammalian cells: A real-time analysis

2006 ◽  
Vol 401 (1-2) ◽  
pp. 44-48 ◽  
Author(s):  
Keigo Nishii ◽  
Iori Yamanaka ◽  
Maya Yasuda ◽  
Yota B. Kiyohara ◽  
Yoko Kitayama ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Circadian Clock ◽  
Real Time ◽  
Mammalian Cells ◽  
Time Analysis ◽  
Real Time Analysis ◽  
Post Transcriptional Regulation ◽  
Clock Protein

scholarly journals Regulatory signals in messenger RNA: determinants of nutrient–gene interaction and metabolic compartmentation

1998 ◽  
Vol 80 (4) ◽  
pp. 307-321
Author(s):  
John E. Hesketh ◽  
M. Helena Vasconcelos ◽  
Giovanna Bermano
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Transcriptional Control ◽  
Regulation Of Gene Expression ◽  
Untranslated Regions ◽  
Nutritional Requirements ◽  
Control Of Gene Expression ◽  
Metabolic Compartmentation ◽  
Post Transcriptional Regulation

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.

Post-transcriptional regulation of gene expression by alternative 5′-untranslated regions in carcinogenesis

2008 ◽  
Vol 36 (4) ◽  
pp. 708-711 ◽  
Author(s):  
Laura Smith
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Cancer Biology ◽  
Regulation Of Gene Expression ◽  
Untranslated Regions ◽  
Specific Distribution ◽  
Eukaryotic Gene ◽  
Multiple Alternative ◽  
Post Transcriptional Regulation ◽  
Inappropriate Expression

Post-transcriptional regulation, via 5′-UTRs (5′-untranslated regions), plays an important role in the control of eukaryotic gene expression. Recent analyses of the mammalian transcriptome suggest that most of the genes express multiple alternative 5′-UTRs and inappropriate expression of these regions has been shown to contribute to the development of carcinogenesis. The present review will focus on the complex post-transcriptional regulation of ERβ (oestrogen receptor β) expression. In particular, results from our laboratory suggest that the expression of alternative 5′-UTRs plays a key role in determining the level of ERβ protein expression. We have also shown that these alternative ERβ 5′-UTRs have a tissue-specific distribution and are differentially expressed between various normal and tumour tissues. Our results also suggest that alternative 5′-UTRs can influence downstream splicing events, thereby perhaps affecting ERβ function. These results suggest that alternative 5′-UTRs may have an overall influence on ER activity and this may have important implications for our understanding of cancer biology and treatment.

scholarly journals Up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) expression is a part of proliferative but not anabolic response of mouse kidney.

2002 ◽  
Vol 49 (4) ◽  
pp. 969-977 ◽  
Author(s):  
Magdalena Dudkowska ◽  
Agnieszka Stachurska ◽  
Barbara Grzelakowska-Sztabert ◽  
Małgorzata Manteuffel-Cymborowska
Keyword(s):  
Transcriptional Regulation ◽  
Expression Pattern ◽  
Proliferative Response ◽  
Experimental Models ◽  
Mouse Kidney ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Differential Expression Pattern ◽  
Post Transcriptional Regulation ◽  
Ssat Activity

A differential expression pattern of spermidine/spermine N(1)-acetyltransferase (SSAT), the enzyme critical to proper homeostasis of cellular polyamines, is reported in mouse kidney undergoing hyperplasia and hypertrophy. We have shown that SSAT activity and SSAT mRNA are significantly induced by antifolate CB 3717 and folate that evoke a drug-injury-dependent hyperplasia. In contrast, SSAT activity is down-regulated in the testosterone-induced hypertrophic kidney, while SSAT mRNA is positively controlled by this androgen. Catecholamine depletion evoked by reserpine drastically decreases the folate-induced activity of S-adenosylmethionine decarboxylase (AdoMetDC), which limits polyamine biosynthesis, but has no effect on SSAT activity augmented by CB 3717. Our results document that the increased SSAT expression solely accompanies the proliferative response of mouse kidney, and suggest the importance of post-transcriptional regulation to the control of SSAT activity in both hyperplastic and hypertrophic experimental models.

scholarly journals Comprehensive analysis of mRNA poly(A) tail reveals complex and conserved regulation

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Hu Nie ◽  
Yiwei Zhang ◽  
Falong Lu ◽  
Jiaqiang Wang
Keyword(s):  
Transcriptional Regulation ◽  
Mammalian Cells ◽  
Tail Length ◽  
Comprehensive Analysis ◽  
Full Length ◽  
New Method ◽  
Full Length Cdna ◽  
Simultaneous Evaluation ◽  
Eukaryotic Species ◽  
Post Transcriptional Regulation

Non-templated poly(A) tails are added to the 3′-end of most mRNAs, which have important roles in post-transcriptional regulation. Recent studies have revealed that poly(A) tails are not composed purely of A residues, but also contain U, C and G residues internally and at their 3′-ends, revealing new levels of complexity. However, no method is able to analyze these internal and terminal non-A residues simultaneously. Here, we developed a new method called PAIso-seq2 which captures RNA 3′-ends by direct 3′ adaptor ligation and rRNA removal by CRISPR/Cas9. This method allows simultaneous evaluation of the poly(A) tail length and 5′-end, internal, and 3′-end non-A residues together with the full-length cDNA for a transcript. Applying this method, we achieved the first complete transcriptome-wide 3′ tail map of mRNA within the nuclear and cytoplasmic compartments of mammalian cells, uncovering differences in poly(A) tail length and non-A residues between these two mRNA populations. A survey of diverse eukaryotic species revealed the conservation of a subset of poly(A) tails containing consecutive U residues in the internal positions, whereas those with consecutive C or G residues were of much lower abundance. Together, we established the first method to be able to comprehensively analyze poly(A) tail 5′-end, internal and 3′-end non-A residues in addition to the length simultaneously, and reveal the first complete mRNA 3′ tail map, providing rich insights into the regulatory roles of poly(A) tails.

scholarly journals Post-Transcriptional Circadian Regulation in Macrophages Organizes Temporally Distinct Immunometabolic States

2020 ◽  
Author(s):  
Emily J Collins ◽  
Mariana P Cervantes-Silva ◽  
George A Timmons ◽  
James R O’Siorain ◽  
Annie M Curtis ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Metabolic Regulation ◽  
Time Course ◽  
Mitochondrial Morphology ◽  
Circadian Regulation ◽  
Atp Production ◽  
Post Transcriptional Regulation ◽  
The Impact

SUMMARYOur core timekeeping mechanism, the circadian clock, regulates an astonishing amount of cellular physiology and behavior, playing a vital role in organismal fitness. While the mechanics of circadian control over cellular regulation can in part be explained by the transcriptional activation stemming from the positive arm of the clock’s transcription-translation negative feedback loop, research has shown that extensive circadian regulation occurs beyond transcriptional activation in fungal species and data suggest that this post-transcriptional regulation may also be preserved in mammals. To determine the extent to which circadian output is regulated post-transcriptionally in mammalian cells, we comprehensively profiled the transcriptome and proteome of murine bone marrow-derived macrophages in a high resolution, sample rich time course. We found that only 15% of the circadian proteome had corresponding oscillating mRNA and this regulation was cell intrinsic. Ontological analysis of oscillating proteins revealed robust temporal enrichment for protein degradation and translation, providing potential insights into the source of this extensive post-transcriptional regulation. We noted post-transcriptional temporal-gating across a number of connected metabolic pathways. This temporal metabolic regulation further corresponded with rhythms we observed in ATP production, mitochondrial morphology, and phagocytosis. With the strong interconnection between cellular metabolic states and macrophage phenotypes/responses, our work demonstrates that post-transcriptional circadian regulation in macrophages is broadly utilized as a tool to confer time-dependent immune function and responses. As macrophages coordinate many immunological and inflammatory functions, an understanding of this regulation provides a framework to determine the impact of circadian regulation on a wide array of disease pathologies.

scholarly journals AUUUA is not sufficient to promote poly(A) shortening and degradation of an mRNA: the functional sequence within AU-rich elements may be UUAUUUA(U/A)(U/A).

1994 ◽  
Vol 14 (12) ◽  
pp. 7984-7995 ◽  
Author(s):  
C A Lagnado ◽  
C Y Brown ◽  
G J Goodall
Keyword(s):  
Binding Site ◽  
Mammalian Cells ◽  
Degradation Rate ◽  
Degradation Pathway ◽  
Untranslated Regions ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Two Phases ◽  
The Many ◽  
Rate Limiting

AU-rich elements (AREs) in the 3' untranslated regions of several cytokine and oncogene mRNAs have been shown to function as signals for rapid mRNA degradation, and it is assumed that the many other cytokine and oncogene mRNAs that contain AU-rich sequences in the 3' untranslated region are similarly targeted for rapid turnover. We have used a chimeric gene composed mostly of growth hormone sequences with expression driven by the c-fos promoter to investigate the minimal sequence required to act as a functional destabilizing element and to monitor the effect of these sequences on early steps in the degradation pathway. We find that neither AUUUA, UAUUUA, nor AUUUAU can function as a destabilizing element. However, the sequence UAUUUAU, when present in three copies, is sufficient to destabilize a chimeric mRNA. We propose that this sequence functions by virtue of being a sufficient portion of the larger sequence, UUAUUUA(U/A)(U/A), that we propose forms the optimal binding site for a destabilizing factor. The destabilizing effect depends on the number of copies of this proposed binding site and their degree of mismatch in the first two and last two positions, with mismatches in the AUUUA sequence not being tolerated. We found a strict correlation between the effect of an ARE on degradation rate and the effect on the rate of poly(A) shortening, consistent with deadenylation being the first and rate-limiting step in degradation, and the step stimulated by destabilizing AREs. Deadenylation was observed to occur in at least two phases, with an oligo(A) intermediate transiently accumulating, consistent with the suggestion that the degradation processes may be similar in yeast and mammalian cells. AREs that are especially U rich and contain no UUAUUUA(U/A)(U/A) motifs failed to influence the degradation rate or the deadenylation rate, either when downstream of suboptimal destabilizing AREs or when alone.

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