Regulatory connection II: disconnection and sustainability

Author(s):  
Roger Brownsword ◽  
Morag Goodwin
2021 ◽  
Author(s):  
Yi-Shi Liu ◽  
Yicheng Wang ◽  
Xiaoman Zhou ◽  
LinPei Zhang ◽  
Ganglong Yang ◽  
...  

Abstract We previously reported that glycosylphosphatidylinositol (GPI) biosynthesis is regulated by endoplasmic reticulum associated degradation (ERAD); however, the underlying mechanistic basis remains unclear. Based on a genome-wide CRISPR–Cas9 screen, we show that a widely expressed GPI-anchored protein CD55 precursor and ER-resident ARV1 together upregulate GPI biosynthesis under ERAD-deficient conditions. In cells defective in GPI transamidase, GPI-anchored protein precursors fail to obtain GPI, remaining the uncleaved GPI-attachment signal at the C-termini. We show that ERAD deficiency causes accumulation of the CD55 precursor, which in turn upregulates GPI biosynthesis, where the GPI-attachment signal peptide is the active element. Among the 32 GPI-anchored proteins tested, only the GPI-attachment signal peptides of CD55 and CD48 enhance GPI biosynthesis. ARV1 is essential for the GPI upregulation by CD55 precursor. Our data demonstrate an ARV1-dependent regulatory connection between GPI biosynthesis and precursors of select GPI-anchored proteins that are under the control of ERAD.


Microbiology ◽  
2011 ◽  
Vol 157 (12) ◽  
pp. 3398-3404 ◽  
Author(s):  
Emma Sevilla ◽  
Beatriz Martín-Luna ◽  
Andrés González ◽  
Jesús A. Gonzalo-Asensio ◽  
María Luisa Peleato ◽  
...  

The interplay between Fur (ferric uptake regulator) proteins and small, non-coding RNAs has been described as a key regulatory loop in several bacteria. In the filamentous cyanobacterium Anabaena sp. PCC 7120, a large dicistronic transcript encoding the putative membrane protein Alr1690 and an α-furA RNA is involved in the modulation of the global regulator FurA. In this work we report the existence of three novel antisense RNAs in cyanobacteria and show that a cis α-furA RNA is conserved in very different genomic contexts, namely in the unicellular cyanobacteria Microcystis aeruginosa PCC 7806 and Synechocystis sp. PCC 6803. Syα-fur RNA covers only part of the coding sequence of the fur orthologue sll0567, whose flanking genes encode two hypothetical proteins. Transcriptional analysis of fur and its adjacent genes in Microcystis unravels a highly compact organization of this locus involving overlapping transcripts. Maα-fur RNA spans the whole Mafur CDS and part of the flanking dnaJ and sufE sequences. In addition, Mafur seems to be part of a dicistronic operon encoding this regulator and an α-sufE RNA. These results allow new insights into the transcriptomes of two unicellular cyanobacteria and suggest that in M. aeruginosa PCC 7806, the α-fur and α-sufE RNAs might participate in a regulatory connection between the genes of the dnaJ–fur–sufE locus.


2020 ◽  
Author(s):  
Nina Lämmermann ◽  
Donat Wulf ◽  
Kwang Suk Chang ◽  
Julian Wichmann ◽  
Junhwan Jang ◽  
...  

ABSTRACTSurvival under excess light conditions requires the light-induced accumulation of protein LHCSR3 and other photoprotection factors, to enable efficient energy-dependent quenching in the green microalga Chlamydomonas reinhardtii. Here, we demonstrate that the high light-tolerant phenotype of mutant hit1 is caused by a de-repression of promoters belonging to photoprotection genes, which in turn results from an inactivation of the E3 ubiquitin ligase substrate adaptor LRS1. Transcriptome analyses of hit1 revealed massive alterations of gene expression modulation as a consequence of perturbed LRS1 function, indicating its role as a crown regulator. In conjunction with random forest-based network modeling, these transcriptome analyses predicted that LRS1 controls photoprotection gene expression via an algal HY5 homolog as its prime transcription factor target. CrHY5 binds to T-box elements present in the promoters of these genes and its inactivation in the hit1 mutant via CRISPR-Cas9 genome editing, confirmed the regulatory connection between LRS1 and CrHY5, predicted by the network analysis.


2019 ◽  
Vol 44 (1) ◽  
pp. 85-108 ◽  
Author(s):  
David Neilson

This article brings in the concept of the ‘neoliberal model of development’ as a corrective to the prevailing emphasis in the literature that usefully describes neoliberalism as a nationally diverging phenomenon but does not adequately examine the mid-range trans-national/global regulatory connection or the logics of national convergence. By extending the concept of regulation and specifying the national trans-national connection, this article revises the original Parisian French Regulation School conception of a ‘model of development’ and makes it applicable to the contemporary neoliberal era. It then applies this revised conception to help explain contemporary patterns of national convergence and divergence. In particular, with reference to Marx’s theory of the ‘relative surplus population’, this article explores capitalism’s uneven development as a form of national variation intensified by the neoliberal model of development. This revisionist analysis of model of development also demonstrates how its praxis dimension is significant for explaining past and present mid-range variations of capitalism, and more importantly for making a mid-range counter-hegemonic future.


2017 ◽  
Vol 143 (6) ◽  
pp. 660-670 ◽  
Author(s):  
Nobutaka Takahashi ◽  
Anton N. Shuvaev ◽  
Ayumu Konno ◽  
Yasunori Matsuzaki ◽  
Masashi Watanave ◽  
...  

2003 ◽  
Vol 2 (4) ◽  
pp. 729-736 ◽  
Author(s):  
C. Almaguer ◽  
D. Mantella ◽  
E. Perez ◽  
J. Patton-Vogt

ABSTRACT Glycerophosphoinositol is produced through deacylation of the essential phospholipid phosphatidylinositol. In Saccharomyces cerevisiae, the glycerophosphoinositol produced is excreted from the cell but is recycled for phosphatidylinositol synthesis when inositol is limiting. To be recycled, glycerophosphoinositol enters the cell through the permease encoded by GIT1. The transport of exogenous glycerophosphoinositol through Git1p is sufficiently robust to support the growth of an inositol auxotroph (ino1Δ). We now report that S. cerevisiae also uses exogenous phosphatidylinositol as an inositol source. Evidence suggests that phosphatidylinositol is deacylated to glycerophosphoinositol extracellularly before being transported across the plasma membrane by Git1p. A genetic screen identified Pho86p, which is required for targeting of the major phosphate transporter (Pho84p) to the plasma membrane, as affecting the utilization of phosphatidylinositol and glycerophosphoinositol. Deletion of PHO86 in an ino1Δ strain resulted in faster growth when either phosphatidylinositol or glycerophosphoinositol was supplied as the sole inositol source. The incorporation of radiolabeled glycerophosphoinositol into an ino1Δ pho86Δ mutant was higher than that into wild-type, ino1Δ, and pho86Δ strains. All strains accumulated the most GIT1 transcript when incubated in media limited for inositol and phosphate in combination. However, the ino1Δ pho86Δ mutant accumulated approximately threefold more GIT1 transcript than did the other strains when incubated in inositol-free media containing either high or low concentrations of Pi. Deletion of PHO4 abolished GIT1 transcription in a wild-type strain. These results indicate that the transport of glycerophosphoinositol by Git1p is regulated by factors affecting both inositol and phosphate availabilities and suggest a regulatory connection between phosphate metabolism and phospholipid metabolism.


2018 ◽  
Author(s):  
D. Sean Froese ◽  
Jola Kopec ◽  
Elzbieta Rembeza ◽  
Gustavo Arruda Bezerra ◽  
Anselm Erich Oberholzer ◽  
...  

AbstractThe folate and methionine cycles are crucial to the biosynthesis of lipids, nucleotides and proteins, and production of the global methyl donor S-adenosylmethionine (SAM). 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a key regulatory connection between these cycles, generating 5-methyltetrahydrofolate for initiation of the methionine cycle, and undergoing allosteric inhibition by its end product SAM. Our 2.5 Å resolution crystal structure of human MTHFR reveals a unique architecture, appending the well-conserved catalytic TIM-barrel to a eukaryote-only SAM-binding domain. The latter domain of novel fold provides the predominant interface for MTHFR homo-dimerization, positioning the N-terminal serine-rich phosphorylation region into proximity with the C-terminal SAM-binding domain. This explains how MTHFR phosphorylation, identified on 11 N-terminal residues (16-total), increases sensitivity to SAM binding and inhibition. Finally, we demonstrate the 25-amino-acid inter-domain linker enables conformational plasticity and propose it to be a key mediator of SAM regulation.


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