scholarly journals Proximity to the Promoter and Terminator Regions Regulates the Transcription Enhancement Potential of an Intron

2021 ◽  
Vol 8 ◽  
Author(s):  
Katherine Dwyer ◽  
Neha Agarwal ◽  
Alisa Gega ◽  
Athar Ansari

An evolutionarily conserved feature of introns is their ability to enhance expression of genes that harbor them. Introns have been shown to regulate gene expression at the transcription and post-transcription level. The general perception is that a promoter-proximal intron is most efficient in enhancing gene expression and the effect diminishes with the increase in distance from the promoter. Here we show that the intron regains its positive influence on gene expression when in proximity to the terminator. We inserted ACT1 intron into different positions within IMD4 and INO1 genes. Transcription Run-On (TRO) analysis revealed that the transcription of both IMD4 and INO1 was maximal in constructs with a promoter-proximal intron and decreased with the increase in distance of the intron from the promoter. However, activation was partially restored when the intron was placed close to the terminator. We previously demonstrated that the promoter-proximal intron stimulates transcription by affecting promoter directionality through gene looping-mediated recruitment of termination factors in the vicinity of the promoter region. Here we show that the terminator-proximal intron also enhances promoter directionality and results in compact gene architecture with the promoter and terminator regions in close physical proximity. Furthermore, we show that both the promoter and terminator-proximal introns facilitate assembly or stabilization of the preinitiation complex (PIC) on the promoter. On the basis of these findings, we propose that proximity to both the promoter and the terminator regions affects the transcription regulatory potential of an intron, and the terminator-proximal intron enhances transcription by affecting both the assembly of preinitiation complex and promoter directionality.

2018 ◽  
Author(s):  
Jaclyn M Fingerhut ◽  
Jessica V Moran ◽  
Yukiko Yamashita

Intron gigantism, where genes contain megabase-sized introns, is observed across species, yet little is known about its purpose or regulation. Here we identify a unique gene expression program utilized for the proper expression of genes with intron gigantism. We find that two Drosophila genes with intron gigantism, kl-3 and kl-5, are transcribed in a spatiotemporal manner over the course of spermatocyte differentiation, which spans ~90 hours. The introns of these genes contain megabases of simple satellite DNA repeats that comprise over 99% of the gene loci, and these satellite-DNA containing introns are transcribed. We identify two RNA-binding proteins that specifically localize to kl-3 and kl-5 transcripts and are needed for the successful transcription or processing of these genes. We propose that genes with intron gigantism require a unique gene expression program, which may serve as a platform to regulate gene expression during cellular differentiation.


2020 ◽  
Vol 54 (1) ◽  
pp. 237-264
Author(s):  
Thomas E. Dever ◽  
Ivaylo P. Ivanov ◽  
Matthew S. Sachs

Cells utilize transcriptional and posttranscriptional mechanisms to alter gene expression in response to environmental cues. Gene-specific controls, including changing the translation of specific messenger RNAs (mRNAs), provide a rapid means to respond precisely to different conditions. Upstream open reading frames (uORFs) are known to control the translation of mRNAs. Recent studies in bacteria and eukaryotes have revealed the functions of evolutionarily conserved uORF-encoded peptides. Some of these uORF-encoded nascent peptides enable responses to specific metabolites to modulate the translation of their mRNAs by stalling ribosomes and through ribosome stalling may also modulate the level of their mRNAs. In this review, we highlight several examples of conserved uORF nascent peptides that stall ribosomes to regulate gene expression in response to specific metabolites in bacteria, fungi, mammals, and plants.


2018 ◽  
Author(s):  
Erdem Sendinc ◽  
David Valle-Garcia ◽  
Abhinav Dhall ◽  
Hao Chen ◽  
Telmo Henriques ◽  
...  

SummarymRNA modifications play an important role in regulating gene expression. One of the most abundant mRNA modifications is N6,2-O-dimethyladenosine (m6Am). Here, we demonstrate that m6Am is an evolutionarily conserved mRNA modification mediated by the Phosphorylated CTD Interacting Factor 1 (PCIF1), which catalyzes m6A methylation on 2-O-methylated adenine located at the 5’ ends of mRNAs. Furthermore, PCIF1 catalyzes only 5’ m6Am methylation of capped mRNAs, but not internal m6A methylation in vitro and in vivo. Our global mRNA methylation analysis revealed that there is no crosstalk between m6Am and m6A mRNA methylation events, suggesting that m6Am is functionally distinct from m6A. Importantly, our data indicate that m6Am negatively impacts translation of methylated mRNAs by antagonizing cap binding protein eIF4E. Together, we identify the first and only human mRNA m6Am methyltransferase and demonstrate a novel mechanism of gene expression regulation through PCIF1-mediated m6Am mRNA methylation in eukaryotes.HighlightsPCIF1 is an evolutionarily conserved mRNA m6Am methyltransferaseLoss of PCIF1 leads to a complete loss of m6Am, whereas m6A level and distribution are not affectedPCIF1 mediated m6Am does not affect RNA Pol II transcription or mRNA stabilitym6Am-Exo-Seq is a robust methodology that enables global m6Am mappingm6Am suppresses cap dependent translation


2021 ◽  
Author(s):  
Hyung Don Ryoo ◽  
Huai-Wei Huang

Retinoids act as chromophore co-factors for light-detecting rhodopsin proteins. In vertebrates, retinoids also actively regulate gene expression. Whether retinoids regulate gene expression in  Drosophila for a specific biological function remains unclear. Here, we report that  Drosophila fatty acid binding protein ( fabp ) is a retinoid-inducible gene required for Rhodopsin-1 (Rh1) protein homeostasis and photoreceptor survival. Specifically, we performed a photoreceptor-specific gene expression profiling study in flies bearing a misfolding-prone Rhodopsin-1 (Rh1) mutant,  ninaE G69D , which serves as a  Drosophila  model for Retinitis Pigmentosa.  ninaE G69D photoreceptors showed increased expression of genes that control Rh1 protein levels, along with a poorly characterized gene, fabp . We found that in vivo  fabp  expression was reduced when the retinoids were deprived through independent methods. Conversely,  fabp  mRNA was induced when we challenged cultured  Drosophila cells with retinoic acid. In flies reared under light, loss of  fabp  caused an accumulation of Rh1 proteins in cytoplasmic vesicles.  fabp  mutants exhibited light-dependent retinal degeneration, a phenotype also found in other mutants that block light-activated Rh1 degradation. These observations indicate that a retinoid-inducible gene expression program regulates  fabp  that is required forRh1 proteostasis and photoreceptor survival.


2013 ◽  
Vol 35 (5) ◽  
pp. 587-594 ◽  
Author(s):  
Jun-Fang ZHANG ◽  
Hua-Bin ZHU ◽  
Liu-Guang ZHANG ◽  
Hai-Sheng HAO ◽  
Xue-Ming ZHAO ◽  
...  

1992 ◽  
Vol 66 (1) ◽  
pp. 95-105 ◽  
Author(s):  
A M Colberg-Poley ◽  
L D Santomenna ◽  
P P Harlow ◽  
P A Benfield ◽  
D J Tenney

2019 ◽  
Vol 70 (19) ◽  
pp. 5355-5374 ◽  
Author(s):  
Dandan Zang ◽  
Jingxin Wang ◽  
Xin Zhang ◽  
Zhujun Liu ◽  
Yucheng Wang

Abstract Plant heat shock transcription factors (HSFs) are involved in heat and other abiotic stress responses. However, their functions in salt tolerance are little known. In this study, we characterized the function of a HSF from Arabidopsis, AtHSFA7b, in salt tolerance. AtHSFA7b is a nuclear protein with transactivation activity. ChIP-seq combined with an RNA-seq assay indicated that AtHSFA7b preferentially binds to a novel cis-acting element, termed the E-box-like motif, to regulate gene expression; it also binds to the heat shock element motif. Under salt conditions, AtHSFA7b regulates its target genes to mediate serial physiological changes, including maintaining cellular ion homeostasis, reducing water loss rate, decreasing reactive oxygen species accumulation, and adjusting osmotic potential, which ultimately leads to improved salt tolerance. Additionally, most cellulose synthase-like (CSL) and cellulose synthase (CESA) family genes were inhibited by AtHSFA7b; some of them were randomly selected for salt tolerance characterization, and they were mainly found to negatively modulate salt tolerance. By contrast, some transcription factors (TFs) were induced by AtHSFA7b; among them, we randomly identified six TFs that positively regulate salt tolerance. Thus, AtHSFA7b serves as a transactivator that positively mediates salinity tolerance mainly through binding to the E-box-like motif to regulate gene expression.


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