Journal: International Journal of Molecular Sciences

Article Title: Integrated Symbiotic Pleiotropy: Long Non-Coding RNAs and Disordered Proteins Interweaving the Functional Layers of the Eukaryotic Cell

doi: 10.3390/ijms27083478

Figure Lengend Snippet: Evolutionary trajectory of TERT: from rigid catalyst to liquid-state driver. ( A ) Structural stability in invertebrates: The TERT ortholog from T. castaneum (PDB ID: 7QKM) represents the ancestral, predominantly ordered state. FuzDrop profiling reveals a low droplet-promoting probability (p LLPS : 0.11), where the protein acts as a rigid enzymatic unit. ( B ) LLPS expansion in mammals: Human TERT exhibits a significant rise in intrinsic disorder (31.43%) and p LLPS (0.62). Domain mapping shows that liquidity peaks coincide with RNA-interacting motifs (GQ, CP, and QFP) and the Nuclear Localization Signal (NLS), suggesting that in higher eukaryotes, TERT functions as an active organizer of telomeric condensates. ( C ) The “L-paradox” across taxa: Large-scale analysis reveals that while intrinsic disorder remains relatively conserved (28–38% across vertebrates), the propensity for phase separation (pLLPS) exhibits sharp, lineage-specific oscillations. This “L-paradox” (liquidity paradox) indicates that phase behavior acts as an evolutionary “switch” or rheostat, with outliers like the lamprey and domestic cat (marked with red stars) showing extreme spikes in liquidity. This variability likely reflects lineage-specific adaptations in genomic maintenance, metabolic rate, and cellular longevity.

Article Snippet: Taxon-dependent clustering: Our results show clear phylogenetic clustering of p LLPS values ( C).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Integrated Symbiotic Pleiotropy: Long Non-Coding RNAs and Disordered Proteins Interweaving the Functional Layers of the Eukaryotic Cell

doi: 10.3390/ijms27083478

Figure Lengend Snippet: Biophysical landscapes of Arc orthologs and Gag-related proteins. (Top) 3D structures (PDB), residue-based droplet-promoting probabilities (p DP ), predicted regions of disorder, aggregation, and context-dependent binding (FuzDrop/FuzPred), and UniProt domains/features aligned with the p DP graph of ( A ) D. melanogaster (dArc2) and ( B ) H. sapiens (Arc), illustrating the evolutionary transition from rigid invertebrate architecture to high-disorder and LLPS propensity mammalian condensates. (Bottom) ( C ) Comparative analysis of p LLPS propensity, protein disorder, and amyloidogenic potential across 30+ species. Left Y-axis: p LLPS and disorder scores (0.0–1.0). Right Y-axis: Number of amyloidogenic segments (PASTA 2.0). Yellow/Pink bars: Evolutionary benchmarks (HIV-1 Gag, PERV Gag, and PEG10) revealing the high ancestral propensity for phase separation and aggregation. Light-blue bars: Drosophila convergent homologs (dArc1, dArc2); dark-blue bars: vertebrate orthologs, highlighting the significant “mammalian shift” in p LLPS . Red dots: Amyloidogenic potential, showing discrete “quantal” plateaus (7–8 for Sauropsids vs. 38 for Eutherians). Stars: Red and blue stars denote significant outliers in amyloidogenic potential (notably the Indian elephant) and p LLPS propensity, respectively. Note: The proposed evolutionary trajectories and “quantum leaps” of these biophysical parameters are discussed in detail within the main text .

Article Snippet: Taxon-dependent clustering: Our results show clear phylogenetic clustering of p LLPS values ( C).

Techniques: Residue, Binding Assay