scholarly journals Structural basis for gene regulation by a B12-dependent photoreceptor

Nature ◽  
2015 ◽  
Vol 526 (7574) ◽  
pp. 536-541 ◽  
Author(s):  
Marco Jost ◽  
Jésus Fernández-Zapata ◽  
María Carmen Polanco ◽  
Juan Manuel Ortiz-Guerrero ◽  
Percival Yang-Ting Chen ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Structural Basis

scholarly journals Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch

Nature ◽  
2006 ◽  
Vol 441 (7097) ◽  
pp. 1167-1171 ◽  
Author(s):  
Alexander Serganov ◽  
Anna Polonskaia ◽  
Anh Tuân Phan ◽  
Ronald R. Breaker ◽  
Dinshaw J. Patel
Keyword(s):  
Gene Regulation ◽  
Thiamine Pyrophosphate ◽  
Structural Basis

scholarly journals An Overview of the Importance of Conformational Flexibility in Gene Regulation by the Transcription Factors

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Shagufta H. Khan ◽  
Raj Kumar
Keyword(s):  
Gene Regulation ◽  
Transcription Factors ◽  
Target Genes ◽  
Conformational Flexibility ◽  
Structural Basis ◽  
Biological Functions ◽  
Multiprotein Complexes ◽  
Cellular Processes ◽  
Intrinsically Disordered ◽  
Coregulatory Proteins

A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors. Available evidences suggest that presence of ID region/domain within a transcription factor plays an important role in its biological functions. These ID sequences provide large flexible surfaces that can allow them to make more efficient physical and functional interactions with their target partners. Since transcription factors regulate expression of target genes by interacting with specific coregulatory proteins, these ID regions/domains can be used as a platform for such large macromolecular interactions, and may represent a mechanism for regulation of cellular processes. The precise structural basis for the function of these ID regions/domains of the transcription factors remains to be determined. In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built. These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.

scholarly journals Structural basis of hypoxic gene regulation by the Rv0081 transcription factor ofMycobacterium tuberculosis

2018 ◽  
Author(s):  
Ashwani Kumar ◽  
Swastik Phulera ◽  
Arshad Rizvi ◽  
Parshuram Sonawane ◽  
Hemendra Singh Panwar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crystal Structure ◽  
Gene Regulation ◽  
Transcription Factor ◽  
Dna Binding ◽  
Metal Binding ◽  
Transcriptional Regulator ◽  
Tuberculosis Infection ◽  
Structural Basis ◽  
Latent Phase

ABSTRACTThe transcription factor Rv0081 ofM. tuberculosiscontrols the hypoxic gene expression and acts as a regulatory hub in the latent phase of tuberculosis infection. We report here the crystal structure of Rv0081 at 3.3 Å resolution revealing that it belongs to the well-known ArsR/SmtB family proteins. ArsR/SmtB family transcriptional repressors exert gene regulation by reversible metal binding. Hypoxia in general is sensed by bacterial transcriptional regulators via metals or Cys-mediated thiol switches. Oxygen sensing typically leads to transcriptional repressor changing its conformational state with altered DNA-binding property under different oxygen levels. Surprisingly Rv0081 neither has a metal binding domain nor does it possess Cys residues suggesting an alternate mechanism of gene regulation. Our structural analysis identified Ser 48, Ser 49, Ser 52 and Gln 53 as potential residues of Rv0081 involved in DNA binding. We probed DNA-binding of Rv0081 with electrophoretic mobility shift assay (EMSA) as well as surface plasmon resonance (SPR), where the Alanine mutants of these residues showed diminished DNA binding. Similarly, Aspartate mutants of these Ser residues was shown to fail to bind to DNA. Since, phosphorylation of various regulatory proteins is one of the important controlling mechanisms, we expected the role of Ser-phosphorylation of Rv0081 in hypoxic condition. Probing Rv0081 with anti-phosphoserine antibodies inM. tuberculosiscell lysate showed marked enhancement in the phosphorylation of Rv0081 protein under hypoxia. Overall, our structural and biochemical analysis provides the molecular basis for the regulation of Rv0081 in the latent phase of tuberculosis infection.IMPORTANCETuberculosis is one of the deadliest infectious diseases caused by the bacteriumMycobacterium tuberculosis. In about 90% of the infected people,M. tuberculosisexists in a dormant or a latent stage which can be reactivated in favorable conditions. Hypoxia (low oxygen pressure) is one of causes of dormancy. Understanding hypoxic gene regulation inM. tuberculosisis therefore an important step to understand latency. Rv0081 is a transcriptional regulator of genes expressed during hypoxia. In order to understand the mechanism by which Rv00081 regulates gene expression during hypoxia, we have solved the crystal structure of Rv0081 and identified amino acid residues which are critical in its transcriptional regulator activity. The crystal structure is suggestive of mechanism of gene regulation under hypoxia.

Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation

2014 ◽  
Vol 21 (8) ◽  
pp. 671-678 ◽  
Author(s):  
Andreas Schlundt ◽  
Gitta A Heinz ◽  
Robert Janowski ◽  
Arie Geerlof ◽  
Ralf Stehle ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Structural Basis ◽  
Rna Recognition ◽  
Transcriptional Gene Regulation

scholarly journals Structural basis of hypoxic gene regulation by the Rv0081 transcription factor ofMycobacterium tuberculosis

FEBS Letters ◽  
2019 ◽  
Vol 593 (9) ◽  
pp. 982-995 ◽  
Author(s):  
Ashwani Kumar ◽  
Swastik Phulera ◽  
Arshad Rizvi ◽  
Parshuram J. Sonawane ◽  
Hemendra S. Panwar ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Structural Basis ◽  
Ofmycobacterium Tuberculosis

Structural basis for multiple gene regulation by human DUX4

2018 ◽  
Vol 505 (4) ◽  
pp. 1161-1167 ◽  
Author(s):  
Yangyang Li ◽  
Baixing Wu ◽  
Hehua Liu ◽  
Yanqing Gao ◽  
Chun Yang ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Structural Basis ◽  
Multiple Gene

scholarly journals Direct molecular evidence for an ancient, conserved developmental toolkit controlling post-transcriptional gene regulation in land plants

2021 ◽  
Author(s):  
Haiyan Jia ◽  
Kelsey Aadland ◽  
Oralia Kolaczkowski ◽  
Bryan Kolaczkowski
Keyword(s):  
Gene Regulation ◽  
Transcriptional Regulation ◽  
Plant Development ◽  
Evolutionary History ◽  
Flowering Plant ◽  
Structural Basis ◽  
Double Stranded Rna ◽  
High Affinity ◽  
History Of ◽  
Post Transcriptional Regulation

ABSTRACTRNA interference (RNAi) plays important roles in organism development through post-transcriptional regulation of specific target mRNAs. Target specificity is largely controlled by base-pair complementarity between micro-RNA (miRNA) regulatory elements and short regions of the target mRNA. The pattern of miRNA production in a cell interacts with the cell’s mRNA transcriptome to generate a specific network of post-transcriptional regulation that can play critical roles in cellular metabolism, differentiation, tissue/organ development and developmental timing. In plants, miRNA production is orchestrated in the nucleus by a suite of proteins that control transcription of the pri-miRNA gene, post-transcriptional processing and nuclear export of the mature miRNA. In the model plant, Arabidopsis thaliana, post-transcriptional processing of miRNAs is controlled by a pair of physically-interacting proteins, HYL1 and DCL1. However, the evolutionary history of the HYL1-DCL1 interaction is unknown, as is its structural basis. Here we use ancestral sequence reconstruction and functional characterization of ancestral HYL1 in vitro and in vivo to better understand the origin and evolution of the HYL1-DCL1 interaction and its impact on miRNA production and plant development. We found the ancestral plant HYL1 evolved high affinity for both double-stranded RNA (dsRNA) and its DCL1 partner very early in plant evolutionary history, before the divergence of mosses from seed plants (~500 Ma), and these high-affinity interactions remained largely conserved throughout plant evolutionary history. Structural modeling and molecular binding experiments suggest that the second of two double-stranded RNA-binding motifs (DSRMs) in HYL1 may interact tightly with the first of two C-terminal DCL1 DSRMs to mediate the HYL1-DCL1 physical interaction necessary for efficient miRNA production. Transgenic expression of the nearly 200 Ma-old ancestral flowering-plant HYL1 in A. thaliana was sufficient to rescue many key aspects of plant development disrupted by HYL1− knockout and restored near-native miRNA production, suggesting that the functional partnership of HYL1-DCL1 originated very early in and was strongly conserved throughout the evolutionary history of terrestrial plants. Overall, our results are consistent with a model in which miRNA-based gene regulation evolved as part of a conserved plant ‘developmental toolkit’; its role in generating developmental novelty is probably related to the relatively rapid evolution of miRNA genes.

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