Feature Identification of Compensatory Gene Pairs without Sequence Homology in Yeast

Peng, Chieh Yu; Lin, Shu-Hsi; Peng, Shih-Chi; Lyu, Ping‐Chiang; Arita, Masanori; Tang, Chuan-Yi

doi:10.1155/2012/653174

Cited by 2 publications

(1 citation statement)

References 57 publications

(84 reference statements)

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“…rgma maternal-zygotic homozygous mutant lines generated using CRISPR/Cas9 genome editing (gRNAs targeting rgma exon 2 exclusively) appeared phenotypically WT (data not shown), a likely consequence of compensatory mechanisms that have been frequently reported, including upregulation of paralogs (Hartman et al, 2001;Gu et al, 2003;Conant and Wagner, 2004;Hanada et al, 2011;Sztal et al, 2018;To and Andrechek, 2018), nonhomologous genes (Peng et al, 2012;Li et al, 2014), and exon-skipping (Oda et al, 2016;Anderson et al, 2017;Moulton, 2017;Sharpe and Cooper, 2017). However, high-resolution melt analysis revealed that gRNAs targeting rgma exons 2 or 3 generated indels at high frequency ( Fig.…”

Section: Tools For Knocking Down Rgma and Neo1mentioning

confidence: 88%

Rgma-Induced Neo1 Proteolysis Promotes Neural Tube Morphogenesis

et al. 2019

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Neuroepithelial cell (NEC) elongation is one of several key cell behaviors that mediate the tissue-level morphogenetic movements that shape the neural tube (NT), the precursor of the brain and spinal cord. However, the upstream signals that promote NEC elongation have been difficult to tease apart from those regulating apico-basal polarity and hingepoint formation, due to their confounding interdependence. The Repulsive Guidance Molecule a (Rgma)/Neogenin 1 (Neo1) signaling pathway plays a conserved role in NT formation (neurulation) and is reported to regulate both NEC elongation and apico-basal polarity, through signal transduction events that have not been identified. We examine here the role of Rgma/Neo1 signaling in zebrafish (sex unknown), an organism that does not use hingepoints to shape its hindbrain, thereby enabling a direct assessment of the role of this pathway in NEC elongation. We confirm that Rgma/Neo1 signaling is required for microtubule-mediated NEC elongation, and demonstrate via cell transplantation that Neo1 functions cell autonomously to promote elongation. However, in contrast to previous findings, our data do not support a role for this pathway in establishing apical junctional complexes. Last, we provide evidence that Rgma promotes Neo1 glycosylation and intramembrane proteolysis, resulting in the production of a transient, nuclear intracellular fragment (NeoICD). Partial rescue of Neo1a and Rgma knockdown embryos by overexpressing neoICD suggests that this proteolytic cleavage is essential for neurulation. Based on these observations, we propose that RGMA-induced NEO1 proteolysis orchestrates NT morphogenesis by promoting NEC elongation independently of the establishment of apical junctional complexes.

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Section: Tools For Knocking Down Rgma and Neo1mentioning

confidence: 88%

Rgma-Induced Neo1 Proteolysis Promotes Neural Tube Morphogenesis

et al. 2019

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Improved lovastatin production by inhibiting (+)-geodin biosynthesis in Aspergillus terreus

et al. 2019

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Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heartrelated diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or lowvalue feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)geodin as a by-product. An A. terreus mutant strain was developed (gedCΔ) with a disrupted (+)-geodin biosynthesis pathway. The gedCΔ mutant was created by inserting the antibiotic marker hygromycin B (hyg) within the gedC gene that encodes emodin anthrone polyketide synthase (PKS), a primary gene responsible for initiating (+)-geodin biosynthesis. The effects of emodin anthrone PKS gene disruption on (+)-geodin and lovastatin biosynthesis and the production of the precursors acetyl-CoA and malonyl-CoA were investigated with cultures based on glycerol alone and in combination with lactose. The gedCΔ strain showed improved lovastatin production, particularly when cultivated on the glycerol-lactose mixture, increasing lovastatin production by 80% (113 mg/L) while simultaneously inhibiting (+)-geodin biosynthesis compared to the wild-type strain. This study thus shows that suppression of the (+)-geodin pathway increases lovastatin yield and demonstrates a practical approach of manipulating carbon flux by modulating enzyme activity.

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Feature Identification of Compensatory Gene Pairs without Sequence Homology in Yeast

Cited by 2 publications

References 57 publications

Rgma-Induced Neo1 Proteolysis Promotes Neural Tube Morphogenesis

Rgma-Induced Neo1 Proteolysis Promotes Neural Tube Morphogenesis

Improved lovastatin production by inhibiting (+)-geodin biosynthesis in Aspergillus terreus

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