Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase

Zhang, Fangliang; Patel, Dhruti; Colavita, Kristen; Rodionova, Irina A.; Buckley, Brian; Scott, David A.; Kumar, Akhilesh; Shabalina, Svetlana A.; Saha, Swati; Chernov, Mikhail V.; Osterman, Andrei L.; Kashina, Anna

doi:10.1038/ncomms8517

Cited by 36 publications

(33 citation statements)

References 25 publications

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“…These highly stable elements even appear to play different roles in post-translational modifications and protein functions, for example, in actin (48) and prosphorybosyl pyrophosphate synthase (47). Correlations between protein and mRNA structures have been recently demonstrated for several specific cases of mRNAs with experimentally characterized structures (78,97,98).…”

Section: Discussionmentioning

confidence: 99%

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Role of mRNA structure in the control of protein folding

et al. 2016

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Specific structures in mRNA modulate translation rate and thus can affect protein folding. Using the protein structures from two eukaryotes and three prokaryotes, we explore the connections between the protein compactness, inferred from solvent accessibility, and mRNA structure, inferred from mRNA folding energy (ΔG). In both prokaryotes and eukaryotes, the ΔG value of the most stable 30 nucleotide segment of the mRNA (ΔGmin) strongly, positively correlates with protein solvent accessibility. Thus, mRNAs containing exceptionally stable secondary structure elements typically encode compact proteins. The correlations between ΔG and protein compactness are much more pronounced in predicted ordered parts of proteins compared to the predicted disordered parts, indicative of an important role of mRNA secondary structure elements in the control of protein folding. Additionally, ΔG correlates with the mRNA length and the evolutionary rate of synonymous positions. The correlations are partially independent and were used to construct multiple regression models which explain about half of the variance of protein solvent accessibility. These findings suggest a model in which the mRNA structure, particularly exceptionally stable RNA structural elements, act as gauges of protein co-translational folding by reducing ribosome speed when the nascent peptide needs time to form and optimize the core structure.

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Section: Discussionmentioning

confidence: 99%

“…In particular, translation-dependent regulation of post-translational protein arginylation mediated by synonymous codon usage has been demonstrated for the purine nucleotide biosynthesis enzyme PRPS2 (47) and for actins (48). …”

Section: Introductionmentioning

confidence: 99%

Role of mRNA structure in the control of protein folding

et al. 2016

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“…This type of protein modification differentially modulates translation and expression of protein isoforms, such as β‐ and γ‐actin (Kashina ) and phosphoribosyl pyrophosphate synthases (PRPS1 and PRPS2) (Zhang et al . ). The observed modulation by ATE1 of stability and/or activity of proteins that play essential roles in cellular physiology reflects the biological importance of post‐translational protein arginylation.…”

Section: Ate1 Function and Its Physiological Roles In The Nervous Systemmentioning

confidence: 97%

Post‐translational protein arginylation in the normal nervous system and in neurodegeneration

Galiano

Goitea

Hallak

2016

Journal of Neurochemistry

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Post-translational arginylation of proteins is an important regulator of many physiological pathways in cells. This modification was originally noted in protein degradation during neurodegenerative processes, with an apparently different physiological relevance between central and peripheral nervous system. Subsequent studies have identified a steadily increasing number of proteins and proteolysis-derived polypeptides as arginyltransferase (ATE1) substrates, including b-amyloid, a-synuclein, and TDP43 proteolytic fragments. Arginylation is involved in signaling processes of proteins and polypeptides that are further ubiquitinated and degraded by the proteasome. In addition, it is also implicated in autophagy/ lysosomal degradation pathway. Recent studies using mutant mouse strains deficient in ATE1 indicate additional roles of this modification in neuronal physiology. As ATE1 is capable of modifying proteins either at the N-terminus or middle-chain acidic residues, determining which proteins function are modulated by arginylation represents a big challenge. Here, we review studies addressing various roles of ATE1 activity in nervous system function, and suggest future research directions that will clarify the role of post-translational protein arginylation in brain development and various neurological disorders.

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“…As such, many rounds of trial and error are needed to find an optimal dilution for every single condition. Furthermore, ATE1-KO is known to increase cellular sensitivity to HPRT reagent 6-TG, and is therefore expected to generate false-negative responses for this assay (Zhang et al, 2015a). These above problems make the ATE1-KO MEF highly unsuitable for the HPRT assay but should not adversely affect the CherryOFF-GFP reporter.…”

Section: Resultsmentioning

confidence: 99%

A Rapid and Precise Mutation-Activated Fluorescence Reporter for Analyzing Acute Mutagenesis Frequency

Birnbaum

Nemzow

Kumar

et al. 2018

Cell Chemical Biology

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Mutagenesis reporters are critical for quantifying genome stability. However, current methods rely on cell survival/death to report mutation, which takes weeks and prevents evaluation of acute or time-dependent changes. Existing methods also have other limitations, such as cell type restrictions. Using our discovery that mCherryFP fluorescence depends on residue Trp98, we replaced this codon with a stop codon to generate a mutation biosensor (termed CherryOFF), with a green fluorescence protein (GFP) as an internal control. We found that the red fluorescence of this biosensor is activated by a specific A/T-G/C nucleotide transition. Compared with the established hypoxanthine phosphoribosyl transferase assay, our reporter has similar or better ability to detect changes of mutation frequency induced by physical/chemical mutagens or manipulation of mutation-related genes. Furthermore, CherryOFF-GFP can report mutagenesis independently of cell-death events, can be adapted to many cell types, and can generate readouts within 1 day for the measurement of acute or time-dependent events.

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Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase

Cited by 36 publications

References 25 publications

Role of mRNA structure in the control of protein folding

Role of mRNA structure in the control of protein folding

Post‐translational protein arginylation in the normal nervous system and in neurodegeneration

A Rapid and Precise Mutation-Activated Fluorescence Reporter for Analyzing Acute Mutagenesis Frequency

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