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

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.

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Chromatin-associated protein complexes link DNA base J and transcription termination in Leishmania

10.1101/2020.05.26.117721 ◽

2020 ◽

Author(s):

Bryan C Jensen ◽

Isabelle Q. Phan ◽

Jacquelyn R. McDonald ◽

Aakash Sur ◽

Mark A. Gillespie ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Protein Complexes ◽

Transcription Termination ◽

Critical Role ◽

Regulation Of Gene Expression ◽

Regulation Of Transcription ◽

Control Of Gene Expression ◽

Polycistronic Transcription ◽

Post Transcriptional Regulation

AbstractUnlike most other eukaryotes, Leishmania and other trypanosomatid protozoa have largely eschewed transcriptional control of gene expression; relying instead on post-transcriptional regulation of mRNAs derived from polycistronic transcription units (PTUs). In these parasites, a novel modified nucleotide base (β-D-glucopyranosyloxymethyluracil) known as J plays a critical role in ensuring that transcription termination occurs only at the end of each PTU, rather than at the polyadenylation sites of individual genes. To further understand the biology of J-associated processes, we used tandem affinity purification (TAP-tagging) and mass spectrometry to reveal proteins that interact with the glucosyltransferase performing the final step in J synthesis. These studies identified four proteins reminiscent of subunits in the PTW/PP1 complex that controls transcription termination in higher eukaryotes. Moreover, bioinformatic analyses identified the DNA-binding subunit of Leishmania PTW/PP1 as a novel J-binding protein (JBP3). Down-regulation of JBP3 expression levels in Leishmania resulted in a substantial increase in transcriptional read-through at the 3’ end of most PTUs. Additional TAP-tagging experiments showed that JBP3 also associates with two other protein complexes. One consists of subunits with domains suggestive of a role in chromatin modification/remodeling; while the other contains subunits with similarity to those found in the PAF1 complex involved in regulation of transcription in other eukaryotes. Thus, trypanosomatids utilize protein complexes similar to those used to control transcription termination in other eukaryotes and JBP3 appears to function as a hub linking these modules to base J, thereby enabling the parasites’ unique reliance on polycistronic transcription and post-transcriptional regulation of gene expression.

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Essential Cytoplasmic Role of the Histone Lysine Methyltransferase Setdb1 in Post-Transcriptional Regulation in Embryonic Stem Cells

10.21203/rs.3.rs-145869/v1 ◽

2021 ◽

Author(s):

Roberta Rapone ◽

Laurence Del Maestro ◽

Costas Bouyioukos ◽

Sonia Albini ◽

Paola Cruz-Tapias ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Transcriptional Regulation ◽

Mrna Stability ◽

Regulation Of Gene Expression ◽

Embryonic Stem ◽

Histone Lysine ◽

Histone Lysine Methyltransferase ◽

Lysine Methyltransferase ◽

Post Transcriptional Regulation

Abstract Embryonic stem cells (ESCs) fate is regulated both at transcriptional and post-transcriptional levels. Indeed, several studies showed that, in addition to gene transcription, mRNA stability and protein synthesis are finely tuned and strongly control the ESCs pluripotency and fate changes. An increasing number of RNA-binding proteins (RBPs) involved in post-transcriptional and translational regulation of gene expression has been identified as regulators of ESC identity. The major lysine methyltransferase Setdb1 is essential for the self-renewal and viability of ESCs. Setdb1 was primarily known to methylate the lysine 9 of histone 3 (H3K9) in the nucleus, where it regulates chromatin functions. However, Setdb1 is also massively localized in the cytoplasm, including in mouse ESCs, where its role remains unknown. Here we show that the cytoplasmic Setdb1 (cSetdb1) is essential for the survival of mESCs. Functional assays further demonstrate that cSetdb1 regulates gene expression post-transcriptionally, affecting the abundance of mRNAs and the rate of newly synthetized proteins. A yeast-two-hybrid assay shows that cSetdb1 interacts with several regulators of mRNA stability and protein translation machinery, such as the ESCs-specific E3 ubiquitin ligase and mRNA silencer Trim71/Lin41. Finally, proteomic analyses reveal that cSetdb1 is required for the integrity of Trim71 complexes involved in mRNA metabolism and translation. Altogether, our data uncover the essential cytoplasmic function of a firstly supposed nuclear “histone” lysine methyltransferase, Setdb1, and provide new insights into the cytoplasmic/post-transcriptional regulation of gene expression mediated by a key epigenetic regulator.

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

Biochemical Society Transactions ◽

10.1042/bst0360708 ◽

2008 ◽

Vol 36 (4) ◽

pp. 708-711 ◽

Cited By ~ 24

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.

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Cytoplasmic deadenylation: regulation of mRNA fate

Biochemical Society Transactions ◽

10.1042/bst0381531 ◽

2010 ◽

Vol 38 (6) ◽

pp. 1531-1536 ◽

Cited By ~ 44

Author(s):

Katrin Wiederhold ◽

Lori A. Passmore

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Mrna Stability ◽

Regulation Of Gene Expression ◽

The Other ◽

Mrna Turnover ◽

Functional Roles ◽

Specific Mrnas ◽

Post Transcriptional Regulation ◽

Mrna Fate

The poly(A) tail of mRNA has an important influence on the dynamics of gene expression. On one hand, it promotes enhanced mRNA stability to allow production of the protein, even after inactivation of transcription. On the other hand, shortening of the poly(A) tail (deadenylation) slows down translation of the mRNA, or prevents it entirely, by inducing mRNA decay. Thus deadenylation plays a crucial role in the post-transcriptional regulation of gene expression, deciding the fate of individual mRNAs. It acts both in basal mRNA turnover, as well as in temporally and spatially regulated translation and decay of specific mRNAs. In the present paper, we discuss mRNA deadenylation in eukaryotes, focusing on the main deadenylase, the Ccr4–Not complex, including its composition, regulation and functional roles.

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