Physical Principles and Extant Biology Reveal Roles for RNA-Containing Membraneless Compartments in Origins of Life Chemistry - PubMed (original) (raw)
Physical Principles and Extant Biology Reveal Roles for RNA-Containing Membraneless Compartments in Origins of Life Chemistry
Raghav R Poudyal et al. Biochemistry. 2018.
Abstract
This Perspective focuses on RNA in biological and nonbiological compartments resulting from liquid-liquid phase separation (LLPS), with an emphasis on origins of life. In extant cells, intracellular liquid condensates, many of which are rich in RNAs and intrinsically disordered proteins, provide spatial regulation of biomolecular interactions that can result in altered gene expression. Given the diversity of biogenic and abiogenic molecules that undergo LLPS, such membraneless compartments may have also played key roles in prebiotic chemistries relevant to the origins of life. The RNA World hypothesis posits that RNA may have served as both a genetic information carrier and a catalyst during the origin of life. Because of its polyanionic backbone, RNA can undergo LLPS by complex coacervation in the presence of polycations. Phase separation could provide a mechanism for concentrating monomers for RNA synthesis and selectively partition longer RNAs with enzymatic functions, thus driving prebiotic evolution. We introduce several types of LLPS that could lead to compartmentalization and discuss potential roles in template-mediated non-enzymatic polymerization of RNA and other related biomolecules, functions of ribozymes and aptamers, and benefits or penalties imparted by liquid demixing. We conclude that tiny liquid droplets may have concentrated precious biomolecules and acted as bioreactors in the RNA World.
Figures
Figure 1:
Phase separation in extant biology (left) and prebiotic chemistry (right). Low complexity regions of the LAF-1 helicase protein, charged peptides and RNA are involved in liquid-liquid phase separation inside cells (left). Similar interactions could have produced non-membranous compartments in the primordial earth that partition molecules (right). Spermine/polyU RNA coacervates (top) and PAH-ADP coacervates (bottom).
Figure 2:
Non-associative and associative phase separation. In non-associative phase separation, solutions rich in two “incompatible” aqueous polymers form two distinct crowded phases (left). In associative phase separation, polymers interact and associate to form a very crowded polymer-rich phase and separate from the dilute bulk solution (right).
Figure 3:
Structures of molecules discussed in this perspective that are involved in associative phase separation.
Figure 4:
Coacervates concentrate monomers and polymers A) (left) Centrifugation separates condensed phase from the bulk solution. (middle) Concentration of nucleotides in dilute phase (mM). (right) Concentration of nucleotides in condensed phase (M).
Figure 5:
Multiple mechanisms for RNA partitioning inside membraneless compartments (A) Ddx4 protein condensates differentially exclude long double stranded DNA and RNA while absorbing single stranded nucleic acids and regulatory RNAs (left), ΔGpart= -RTln([in]/[out]), where [in] and [out] are concentrations of nucleotides inside and outside of droplets. Constraints in the interior structures of Ddx4 condensates allow a subset of nucleic acid sizes and structures to be absorbed. (B) PAH-ATP coacervates selectively partition RNAs irrespective of the structures and sizes (left). The mechanism for RNA partitioning is by displacement of ATP.
Figure 6:
Ribozyme catalysis in non-associative phase separated system and Mg2+ partitioning in associative phase separated system. (A) Structure of the hammerhead ribozyme. Ribozyme catalysis was carried out in different dextran:PEG phase volumes. 1:0 (filled black circles), 1:5 (blue squares), 1:12.5 (red diamonds), 1:50 (blue triangles) and 1:100 (inverted green triangles). (B) Magnesium and other catalytic potentials inside complex coacervates. Magnesium associated with ATP is also partitioned inside the PAH-ATP coacervates.
Figure 7:
Molecular and environmental tuning of coacervates (A) and (B) Phosphatase enzyme increase the net positive charge by dephosphorylating RRASpLRRASpL peptide which forms coacervates with polyU RNA. (C) and (D) Kinase enzyme decrease the net positive charge by phosphorylating RRASLRRASL peptide and prevent coacervation with polyU RNA. For (B) and (D) appearance or disappearance of phase-separation is indicated by changes in turbidity measurements. Red trace indicates samples without any enzyme. (E) and (F) Turbidity plots indicating either the appearance or disappearance of PolyU RNA/ Spermine coacervates as a function of temperature.
Figure 8:
Potential contributions of coacervate components to prebiotic catalysis and evolution. (A) Several catalytic strategies used by naturally occurring self-cleaving ribozymes described in ref . (B) Scheme for coacervate-assisted RNA oligomerization and partitioning of larger RNAs.
References
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