Why are essential genes essential? - The essentiality of Saccharomyces genes

Zhang, Zhaojie; Ren, Qun

doi:10.15698/mic2015.08.218

Cited by 39 publications

(27 citation statements)

References 61 publications

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“…The term ‘essential gene’ is one way to assess the relative biological importance of a protein’s functionality. However, the term is discussed further in (28). We scanned our gene sets against the essential gene list by an in house script and conducted enrichment tests by Fischer exact test (using the statistical python module scipy.stats - http://www.scipy.org/).…”

Section: Methodsmentioning

confidence: 99%

Robustness by intrinsically disordered C-termini and translational readthrough

Kleppe

Bornberg‐Bauer

2018

Nucleic Acids Research

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During protein synthesis genetic instructions are passed from DNA via mRNA to the ribosome to assemble a protein chain. Occasionally, stop codons in the mRNA are bypassed and translation continues into the untranslated region (3′-UTR). This process, called translational readthrough (TR), yields a protein chain that becomes longer than would be predicted from the DNA sequence alone. Protein sequences vary in propensity for translational errors, which may yield evolutionary constraints by limiting evolutionary paths. Here we investigated TR in Saccharomyces cerevisiae by analysing ribosome profiling data. We clustered proteins as either prone or non-prone to TR, and conducted comparative analyses. We find that a relatively high frequency (5%) of genes undergo TR, including ribosomal subunit proteins. Our main finding is that proteins undergoing TR are highly expressed and have a higher proportion of intrinsically disordered C-termini. We suggest that highly expressed proteins may compensate for the deleterious effects of TR by having intrinsically disordered C-termini, which may provide conformational flexibility but without distorting native function. Moreover, we discuss whether minimizing deleterious effects of TR is also enabling exploration of the phenotypic landscape of protein isoforms.

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Section: Methodsmentioning

confidence: 99%

Robustness by intrinsically disordered C-termini and translational readthrough

Kleppe

Bornberg‐Bauer

2018

Nucleic Acids Research

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“…Next, we focused our analysis on gene essentiality. Here, we found that essential genes (defined as required for an organismʼs survival 47 ) are enriched in pseudogene parent genes. Specifically, they are approximately three times more abundant among parent genes (Supplementary Table 7).…”

Section: Resultsmentioning

confidence: 95%

Transcriptional activity and strain-specific history of mouse pseudogenes

et al. 2020

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Pseudogenes are ideal markers of genome remodelling. In turn, the mouse is an ideal platform for studying them, particularly with the recent availability of strain-sequencing and transcriptional data. Here, combining both manual curation and automatic pipelines, we present a genome-wide annotation of the pseudogenes in the mouse reference genome and 18 inbred mouse strains (available via the mouse.pseudogene.org resource). We also annotate 165 unitary pseudogenes in mouse, and 303, in human. The overall pseudogene repertoire in mouse is similar to that in human in terms of size, biotype distribution, and family composition (e.g. with GAPDH and ribosomal proteins being the largest families). Notable differences arise in the pseudogene age distribution, with multiple retrotranspositional bursts in mouse evolutionary history and only one in human. Furthermore, in each strain about a fifth of all pseudogenes are unique, reflecting strain-specific evolution. Finally, we find that~15% of the mouse pseudogenes are transcribed, and that highly transcribed parent genes tend to give rise to many processed pseudogenes.

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“…20% of yeast proteins are essential for viability. 612 Of the 4000 disease-linked human proteins in UNIPROT, about 1100 have at least one TM segment. Given that MPs constitute ~25% of the proteome, this seems reasonable.…”

Section: Membrane Protein Misfolding In Human Diseasementioning

confidence: 99%

Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis

et al. 2019

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Advances over the past 25 years have revealed much about how the structural properties of membranes and associated proteins are linked to the thermodynamics and kinetics of membrane protein (MP) folding. At the same time biochemical progress has outlined how cellular proteostasis networks mediate MP folding and manage misfolding in the cell. When combined with results from genomic sequencing, these studies have established paradigms for how MP folding and misfolding are linked to the molecular etiologies of a variety of diseases. This emerging framework has paved the way for the development of a new class of small molecule “pharmacological chaperones” that bind to and stabilize misfolded MP variants, some of which are now in clinical use. In this review, we comprehensively outline current perspectives on the folding and misfolding of integral MPs as well as the mechanisms of cellular MP quality control. Based on these perspectives, we highlight new opportunities for innovations that bridge our molecular understanding of the energetics of MP folding with the nuanced complexity of biological systems. Given the many linkages between MP misfolding and human disease, we also examine some of the exciting opportunities to leverage these advances to address emerging challenges in the development of therapeutics and precision medicine.

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Why are essential genes essential? - The essentiality of Saccharomyces genes

Cited by 39 publications

References 61 publications

Robustness by intrinsically disordered C-termini and translational readthrough

Robustness by intrinsically disordered C-termini and translational readthrough

Transcriptional activity and strain-specific history of mouse pseudogenes

Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis

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