scholarly journals Peptide-Dependent Growth in Yeast via Fine-Tuned Peptide/GPCR-Activated Essential Gene Expression

Biochemistry ◽  
2022 ◽  
Author(s):  
Sonja Billerbeck ◽  
Virginia W. Cornish
Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1089 ◽  
Author(s):  
Rocio Enriquez-Gasca ◽  
Poppy A. Gould ◽  
Helen M. Rowe

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.


Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 227-238 ◽  
Author(s):  
William G Kelly ◽  
SiQun Xu ◽  
Mary K Montgomery ◽  
Andrew Fire

In screening for embryonic-lethal mutations in Caernorhabditis elegans, we defined an essential gene (let-858) that encodes a nuclear protein rich in acidic and basic residues. We have named this product nucampholin. Closely homologous sequences in yeast, plants, and mammals demonstrate strong evolutionary conservation in eukaryotes. Nucampholin resides in all nuclei of C. elegans and is essential in early development and in differentiating tissue. Antisense-mediated depletion of LET-858 activity in early embryos causes a lethal phenotype similar to characterized treatments blocking embryonic gene expression. Using transgene-rescue, we demonstrated the additional requirement for let-858 in the larval germline. The broad requirements allowed investigation of soma-germline differences in gene expression. When introduced into standard transgene arrays, let-858 (like many other C. elegans genes) functions well in soma but poorly in germline. We observed incremental silencing of simple let-858 arrays in thefirstfew generations following transformation and hypothesized that silencing might reflect recognition of arrays as repetitive or heterochromatin-like. To give the transgene a more physiological context, we included an excess of random genomic fragments with the injected DNA. The resulting transgenes show robust expression in both germline and soma. Our results suggest the possibility of concerted mechanisms for silencing unwanted germline expression of repetitive sequences.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jasmine L. Loveland ◽  
David B. Lank ◽  
Clemens Küpper

Chromosomal inversions are structural rearrangements that frequently provide genomic substrate for phenotypic diversity. In the ruff Philomachus pugnax, three distinct male reproductive morphs (Independents, Satellites and Faeders) are genetically determined by a 4.5 Mb autosomal inversion. Here we test how this stable inversion polymorphism affects gene expression in males during the lekking season. Gene expression may be altered through disruptions at the breakpoints and the accumulation of mutations due to suppressed recombination. We used quantitative PCR to measure expression of 11 candidate inversion genes across three different tissues (liver, adrenal glands and gonads) and tested for allelic imbalance in four inversion genes across 12 males of all three morphs (8 Independents, 2 Satellites, 2 Faeders). We quantified transcripts of CENPN, an essential gene disrupted by the inversion at the proximal breakpoint, at different exons distributed near and across the breakpoint region. Consistent with dosage dependent gene expression for the breakpoint gene CENPN, we found that expression in Independents was broadly similar for transcripts segments from inside and outside the inversion regions, whereas for Satellites and Faeders, transcript segments outside of the inversion showed at least twofold higher expression than those spanning over the breakpoint. Within the inversion, observed expression differences for inversion males across all four genes with allele-specific primers were consistent with allelic imbalance. We further analyzed gonadal expression of two inversion genes, HSD17B2 and SDR42E1, along with 12 non-inversion genes related to steroid metabolism and signaling in 25 males (13 Independents, 7 Satellites, 5 Faeders). Although we did not find clear morph differentiation for many individual genes, all three morphs could be separated based on gene expression differences when using linear discriminant analysis (LDA), regardless of genomic location (i.e., inside or outside of the inversion). This was robust to the removal of genes with the highest loadings. Pairwise correlations in the expression of genes showed significant correlations for 9–18 pairs of genes within morphs. However, between morphs, we only found a single association between genes SDR42E1 and AROM for Independents and Satellites. Our results suggest complex and wide-ranging changes in gene expression caused by structural variants.


2020 ◽  
Author(s):  
Lucie Peskova ◽  
Denisa Jurcikova ◽  
Tereza Vanova ◽  
Jan Krivanek ◽  
Michaela Capandova ◽  
...  

AbstractMicroRNAs (miRNAs), a class of small, non-coding RNA molecules represent important regulators of gene expression. Recent reports have implicated their role in the cell specification process acting as “fine-tuners” to ensure the precise gene expression at the specific stage of cell differentiation. Here we used retinal organoids differentiated from human pluripotent stem cells (hPSCs) as a model to closely investigate the role of a sensory organ-specific and evolutionary conserved miR-183/96/182 cluster. Using a miRNA tough decoy approach, we inhibited the miR-183/96/182 cluster in hPSCs. Inhibition of the miRNA cluster resulted in an increased expansion of neuroepithelium leading to abnormal “bulged” neural retina in organoids, associated with upregulation of neural-specific and retinal-specific genes. Importantly, we identified PAX6, a well-known essential gene in neuroectoderm specification, as a target of the miR-183/96/182 cluster members. Taken together, the miR-183/96/182 cluster not only represents an important regulator of PAX6 expression, but it also plays a crucial role in retinal tissue morphogenesis.


2019 ◽  
Author(s):  
Tiffany Chien ◽  
Tetsuhiro Harimoto ◽  
Benjamin Kepecs ◽  
Kelsey Gray ◽  
Courtney Coker ◽  
...  

AbstractThe engineering of microbes spurs biotechnological innovations, but requires control mechanisms to confine growth within defined environments for translation. Here we engineer bacterial growth tropism to sense and grow in response to specified oxygen, pH, and lactate signatures. Coupling biosensors to drive essential gene expression reveals engineered bacterial localization within upper or lower gastrointestinal tract. Multiplexing biosensors in an AND logic-gate architecture reduced bacterial off-target colonization in vivo.


2011 ◽  
Vol 175 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Lauren Jammallo ◽  
Keith Eidell ◽  
Paul H. Davis ◽  
Fay J. Dufort ◽  
Courtney Cronin ◽  
...  

2021 ◽  
Author(s):  
Fei Liu ◽  
Yayun Qin ◽  
Yuwen Huang ◽  
Pan Gao ◽  
Jingzhen Li ◽  
...  

The neural retina leucine zipper (NRL) is an essential gene for the fate determination and differentiation of rod photoreceptors in mammals. Mutations in NRL have been associated with autosomal recessive enhanced S-cone syndrome and autosomal dominant retinitis pigmentosa. However, the exact role of Nrl in regulating the development and maintenance of photoreceptors in zebrafish, a popular animal model used for retinal degeneration and regeneration studies, has not been fully determined. In this study, we generated an nrl knockout zebrafish model by CRISPR-Cas9 technology and observed a surprising phenotype characterized by the reduction but not total elimination of rods and the over-grown of green-cones. By tracing the developmental process of rods, we discovered two waves of rod genesis in zebrafish, emerging at the embryonic stage with an nrl-dependent pattern and the post-embryonic stage with an nrl-independent pattern, respectively. Through bulk and single-cell RNA sequencing, we constructed the gene expression profiles for the whole retinal tissues and each of the retinal cell types in WT and nrl knockout zebrafish. We detected the rod/green-cone intermediate photoreceptors in nrl knockout zebrafish, suggesting that there may be a kind of rod/green-cone bipotent precursors and its fate choice between rod and green-cone is controlled by nrl. Besides, we identified the mafba gene as a novel regulator for nrl-independent rods, based on the cell-type-specific expression pattern and the retinal phenotype of nrl/mafba double knockout zebrafish. Furthermore, the altered photoreceptor compositions and abnormal gene expression caused progressive retinal degeneration and subsequent regeneration in nrl knockout zebrafish. Our work revealed a novel function of mafba gene in rod development and established a more suitable model for the developmental processes and regulatory mechanisms of rod and green-cone photoreceptors in zebrafish.


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