Rab-GDI Complex Dissociation Factor Expressed through Translational Frameshifting in Filamentous Ascomycetes

Malagnac, Fabienne; Fabret, Céline; Prigent, Magali; Rousset, Jean‐Pierre; Namy, Olivier; Silar, Philippe

doi:10.1371/journal.pone.0073772

Cited by 11 publications

(4 citation statements)

References 46 publications

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“…For example, in mammalian cells, it was shown that a translational readthrough can result in the creation of a PTS1 motif for a small fraction (1.8%) of the Lactate Dehydrogenase B (LDHB) protein (Schueren et al , 2014 ) and a small fraction (4%) of Malate Dehydrogenase 1 (MDH1) protein (Hofhuis et al , 2016 ). Other mechanisms to expose a cryptic PTS1 motif include an alternative splicing (Freitag et al , 2012 ) and translational frameshift (Malagnac et al , 2013 ). Hypothetically, any type of manipulation – from cleavage to post‐translational modification can result in a modified C′, which may lead to a creation of a PTS1‐like motif.…”

Section: Discussionmentioning

confidence: 99%

Systematic multi‐level analysis of an organelle proteome reveals new peroxisomal functions

Yifrach

Holbrook-Smith

Bürgi

et al. 2022

Molecular Systems Biology

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Seventy years following the discovery of peroxisomes, their complete proteome, the peroxi-ome, remains undefined. Uncovering the peroxiome is crucial for understanding peroxisomal activities and cellular metabolism. We used high-content microscopy to uncover peroxisomal proteins in the model eukaryote -Saccharomyces cerevisiae. This strategy enabled us to expand the known peroxi-ome by ~40% and paved the way for performing systematic, whole-organellar proteome assays. By characterizing the sub-organellar localization and protein targeting dependencies into the organelle, we unveiled non-canonical targeting routes. Metabolomic analysis of the peroxi-ome revealed the role of several newly identified resident enzymes. Importantly, we found a regulatory role of peroxisomes during gluconeogenesis, which is fundamental for understanding cellular metabolism. With the current recognition that peroxisomes play a crucial part in organismal physiology, our approach lays the foundation for deep characterization of peroxisome function in health and disease.

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Section: Discussionmentioning

confidence: 99%

Systematic multi‐level analysis of an organelle proteome reveals new peroxisomal functions

Yifrach

Holbrook-Smith

Bürgi

et al. 2022

Molecular Systems Biology

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“…In most the frameshifting is into the -1 frame, and in P. anserina the shift site is U_UUU_UCC with a pseudoknot starting just 2 nts 3′ of the shift site but with variation in the stimulatory sequence. In some, however, the frameshifting is into the +1 frame ( 347 ).…”

Section: Free Living Organism Chromosomal Genes Lacking Mobile Predecmentioning

confidence: 99%

Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins¹,

Loughran²,

Bhatt³

et al. 2016

Nucleic Acids Res

266

367

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Genetic decoding is not ‘frozen’ as was earlier thought, but dynamic. One facet of this is frameshifting that often results in synthesis of a C-terminal region encoded by a new frame. Ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational ‘correction’ of problem or ‘savior’ indels. Utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. One class of regulatory frameshifting of stable chromosomal genes governs cellular polyamine levels from yeasts to humans. In many cases of productively utilized frameshifting, the proportion of ribosomes that frameshift at a shift-prone site is enhanced by specific nascent peptide or mRNA context features. Such mRNA signals, which can be 5′ or 3′ of the shift site or both, can act by pairing with ribosomal RNA or as stem loops or pseudoknots even with one component being 4 kb 3′ from the shift site. Transcriptional realignment at slippage-prone sequences also generates productively utilized products encoded trans-frame with respect to the genomic sequence. This too can be enhanced by nucleic acid structure. Together with dynamic codon redefinition, frameshifting is one of the forms of recoding that enriches gene expression.

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“…For example, in mammalian cells, it was shown that a translational readthrough can result in the creation of a PTS1 motif for a small fraction (1.8%) of the Lactate Dehydrogenase B (LDHB) protein (Schueren et al, 2014) and a small fraction (4%) of Malate Dehydrogenase 1 (MDH1) protein (Hofhuis et al, 2016). Other mechanisms to expose a cryptic PTS1 motif include an alternative splicing (Freitag et al, 2012) and translational frameshift (Malagnac et al, 2013). Hypothetically, any type of manipulationfrom cleavage to post-translational modification can result in a modified C', which may lead to a creation of a PTS1-like motif.…”

Section: Discussionmentioning

confidence: 99%

Systematic multi-level analysis of an organelle proteome reveals new peroxisomal functions

Yifrach

Holbrook-Smith

Bürgi

et al. 2021

Preprint

View full text Add to dashboard Cite

Seventy years following the discovery of peroxisomes, their proteome remains undefined. Uncovering the complete peroxisomal proteome, the peroxi-ome, is crucial for understanding peroxisomal activities and cellular metabolism. We used high- content microscopy to uncover the peroxi-ome of the model eukaryote – Saccharomyces cerevisiae. This strategy enabled us to expand the known organellar proteome by ∼40% and paved the way for performing systematic, whole-organellar proteome assays. Coupled with targeted experiments this allowed us to discover new peroxisomal functions. By characterizing the sub-organellar localization and protein targeting dependencies into the organelle, we unveiled non-canonical targeting routes. Metabolomic analysis of the peroxi-ome revealed the role of several newly-identified resident enzymes. Importantly, we found a regulatory role of peroxisomes during gluconeogenesis, which is fundamental for understanding cellular metabolism. With the current recognition that peroxisomes play a crucial part in organismal physiology, our approach lays the foundation for deep characterization of peroxisome function in health and disease.

show abstract

Rab-GDI Complex Dissociation Factor Expressed through Translational Frameshifting in Filamentous Ascomycetes

Cited by 11 publications

References 46 publications

Systematic multi‐level analysis of an organelle proteome reveals new peroxisomal functions

Systematic multi‐level analysis of an organelle proteome reveals new peroxisomal functions

Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Systematic multi-level analysis of an organelle proteome reveals new peroxisomal functions

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