SLIMP: Supervised learning of metabolite-protein interactions from co-fractionation mass spectrometry data

Bm, Zühlke; Em, Sokolowska; Luzarowski, Marcin; Schlossarek, Dennis; Chodasiewicz, Monika; Leniak, Ewa; Skirycz, Aleksandra; Nikoloski, Zoran

doi:10.1101/2021.06.16.448636

Cited by 4 publications

(12 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the combined increased Glu and Glu-containing dipeptides at the same time points in the dark might indicate altered N metabolism (Hildebrandt et al, 2015) along the day under limited C supplied for growth (SD), although dipeptides regulatory roles FIGURE 4 | Pro-Gln/protein interaction network. (A) Pro-Gln interactors were predicted by SLIMP (Zühlke et al, 2021) with a score above 0.5. Protein-protein interactions were imported from STRING (Szklarczyk et al, 2016) based on the experimental and database evidence.…”

Section: Discussionmentioning

confidence: 99%

“…Pro-Gln interactors were retrieved from SLIMP ( Zühlke et al, 2021 ). Protein-protein interactions were imported from STRING ( Szklarczyk et al, 2016 ; Supplementary Table 6 ), and used to build the interaction network of the Pro-Gln interactors into Cytoscape ( Shannon et al, 2003 ; Supplementary Table 7 ).…”

Section: Methodsmentioning

confidence: 99%

“…Targets mentioned in the text are highlighted in red letters. 7 | Parameters used in Cytoscape (Shannon et al, 2003) to build the interaction network of the Pro-Gln interactors retrieved from SLIMP (Zühlke et al, 2021) in Cytoscape. Protein-protein interactions were imported from STRING (Szklarczyk et al, 2016) based on the experimental and database evidence.…”

Section: Fundingmentioning

confidence: 99%

“…By focusing on dipeptides that present an oscillating pattern along the diel cycle in Col-0 only under SD conditions, and always enhanced levels in raptor1b , we have identified a group of 16 dipeptides that can be possibly associated with C-restricted supply. By mining existing protein-metabolite interaction data ( Zühlke et al, 2021 ), we delineated putative protein interactors for a representative dipeptide Pro-Gln. The obtained list included enzymes of C and amino acid metabolism, which are also linked to the TORC-mediated metabolic network.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Proteogenic Dipeptides Are Characterized by Diel Fluctuations and Target of Rapamycin Complex-Signaling Dependency in the Model Plant Arabidopsis thaliana

et al. 2021

Self Cite

View full text Add to dashboard Cite

As autotrophic organisms, plants capture light energy to convert carbon dioxide into ATP, nicotinamide adenine dinucleotide phosphate (NADPH), and sugars, which are essential for the biosynthesis of building blocks, storage, and growth. At night, metabolism and growth can be sustained by mobilizing carbon (C) reserves. In response to changing environmental conditions, such as light-dark cycles, the small-molecule regulation of enzymatic activities is critical for reprogramming cellular metabolism. We have recently demonstrated that proteogenic dipeptides, protein degradation products, act as metabolic switches at the interface of proteostasis and central metabolism in both plants and yeast. Dipeptides accumulate in response to the environmental changes and act via direct binding and regulation of critical enzymatic activities, enabling C flux distribution. Here, we provide evidence pointing to the involvement of dipeptides in the metabolic rewiring characteristics for the day-night cycle in plants. Specifically, we measured the abundance of 13 amino acids and 179 dipeptides over short- (SD) and long-day (LD) diel cycles, each with different light intensities. Of the measured dipeptides, 38 and eight were characterized by day-night oscillation in SD and LD, respectively, reaching maximum accumulation at the end of the day and then gradually falling in the night. Not only the number of dipeptides, but also the amplitude of the oscillation was higher in SD compared with LD conditions. Notably, rhythmic dipeptides were enriched in the glucogenic amino acids that can be converted into glucose. Considering the known role of Target of Rapamycin (TOR) signaling in regulating both autophagy and metabolism, we subsequently investigated whether diurnal fluctuations of dipeptides levels are dependent on the TOR Complex (TORC). The Raptor1b mutant (raptor1b), known for the substantial reduction of TOR kinase activity, was characterized by the augmented accumulation of dipeptides, which is especially pronounced under LD conditions. We were particularly intrigued by the group of 16 dipeptides, which, based on their oscillation under SD conditions and accumulation in raptor1b, can be associated with limited C availability or photoperiod. By mining existing protein-metabolite interaction data, we delineated putative protein interactors for a representative dipeptide Pro-Gln. The obtained list included enzymes of C and amino acid metabolism, which are also linked to the TORC-mediated metabolic network. Based on the obtained results, we speculate that the diurnal accumulation of dipeptides contributes to its metabolic adaptation in response to changes in C availability. We hypothesize that dipeptides would act as alternative respiratory substrates and by directly modulating the activity of the focal enzymes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Fundingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proteogenic Dipeptides Are Characterized by Diel Fluctuations and Target of Rapamycin Complex-Signaling Dependency in the Model Plant Arabidopsis thaliana

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has been shown that 2′,3′-cAMP can bind to RNA-binding motives in the protein sequence of Rbp47b, an SG marker to facilitate SG formation (Kosmacz et al, 2018). Interestingly, it was further confirmed by small molecule-protein complex studies that seven out of the 31 high-confidence 2′, 3′-cAMP targets predicted by SLIMP (Zuhlke et al, 2021) contain an RRM domain. The identified list also contains a plastidial protein CP29, a component of the plastidial SG (Chodasiewicz et al, 2020).…”

Section: Discussionmentioning

confidence: 93%

2’,3’-cAMP treatment mimics stress molecular response inArabidopsis thaliana

Chodasiewicz

Kerber

Górka

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

For many years, 2′,3′-cyclic adenosine monophosphate (2′,3′-cAMP), a positional isomer of the second messenger 3′,5′-cAMP, has not received enough attention. Recent studies have reported that 2′,3′-cAMP exists in plants and might be involved in stress signaling because 1) its level increases upon wounding and 2) it was shown to participate in stress granule formation. Although 2′,3′-cAMP is known as RNA-degradation product, the effect of its accumulation in the cell remains unknown. Here, we unprecedentedly evaluate responses at the transcriptome, metabolome, and proteome levels to the accumulation of 2′,3′-cAMP in Arabidopsis plants. Data revealed that 2′,3′-cAMP is metabolized into adenosine, suggesting that a well-known cyclic nucleotide - adenosine pathway from human cells might exist also in plants. However, the control transcriptomic data indicated that, despite fewer overlaps, responses to 2′,3′-cAMP and to adenosine differ. Analysis of the transcriptome and proteome in response to 2′,3′-cAMP showed similar changes, known as signatures for abiotic stress response. This is further supported by the fact that adding to the role in facilitating of stress granules (SGs) formation, 2′,3′-cAMP induces changes at the level of proteins known as key components of SGs and can also induce movement of processing bodies (PBs) in the cell.

show abstract

2′,3′-cAMP treatment mimics the stress molecular response inArabidopsis thaliana

et al. 2022

Self Cite

View full text Add to dashboard Cite

The role of the RNA degradation product 2’,3’-cyclic adenosine monophosphate (2’,3’-cAMP) is poorly understood. Recent studies have identified 2’,3’-cAMP in plant material and determined its role in stress signaling. The level of 2’,3’-cAMP increases upon wounding, in the dark, and under heat, and 2’,3’-cAMP binding to an RNA-binding protein, Rbp47b, promotes stress granule (SG) assembly. To gain further mechanistic insights into the function of 2’,3’-cAMP, we used a multi-omics approach by combining transcriptomics, metabolomics, and proteomics to dissect the response of Arabidopsis (Arabidopsis thaliana) to 2’,3’-cAMP treatment. We demonstrated that 2’,3’-cAMP is metabolized into adenosine, suggesting that the well-known cyclic nucleotide–adenosine pathway of human cells might also exist in plants. Transcriptomics analysis revealed only minor overlap between 2’,3’-cAMP- and adenosine-treated plants, suggesting that these molecules act through independent mechanisms. Treatment with 2’,3’-cAMP changed the levels of hundreds of transcripts, proteins, and metabolites, many previously associated with plant stress responses, including protein and RNA degradation products, glucosinolates, chaperones, and SG components. Finally, we demonstrated that 2’,3’-cAMP treatment influences the movement of processing bodies, confirming the role of 2’,3’-cAMP in the formation and motility of membraneless organelles.

show abstract

SLIMP: Supervised learning of metabolite-protein interactions from co-fractionation mass spectrometry data

Cited by 4 publications

References 39 publications

Proteogenic Dipeptides Are Characterized by Diel Fluctuations and Target of Rapamycin Complex-Signaling Dependency in the Model Plant Arabidopsis thaliana

Proteogenic Dipeptides Are Characterized by Diel Fluctuations and Target of Rapamycin Complex-Signaling Dependency in the Model Plant Arabidopsis thaliana

2’,3’-cAMP treatment mimics stress molecular response inArabidopsis thaliana

2′,3′-cAMP treatment mimics the stress molecular response inArabidopsis thaliana

Contact Info

Product

Resources

About