Overview
One of the great questions facing humanity is “How did life begin?” It is thought that RNA may have played a major role in the process through the so-called RNA world hypothesis. We are collaborating with Christine Keating’s lab at Penn State to address physical means that may have aided the emergence of life through the localization and improvement of catalysis. We are evaluating compartmentalization driven by aqueous phase separation as a potential physicochemical mechanism to concentrate and help chaperone the folding, multiple turnover, and evolution of rare catalytic RNA molecules. We are also addressing how compartmentalization may facilitate the assembly of progenitor membranes as a step towards protocell formation. Accomplishing these goals will provide insight into the early evolution of life on this and other planets.
A recent advance was observation that concentration of RNA increases ~3,000 fold in the dextran-rich phase of a PEG/dextran aqueous two-phase system (ATPS). We showed that this leads to significant increases in the rate of ribozyme cleavage. This finding emphasizes compartmentalization in the attainment of function in an RNA world as well as modern biology. We also found that droplets from liposome stabilized all-aqueous emulsions act as bioreactors. A major theme of this project is attaining RNA function in protocells that are robust, meaning they can be comprised of diverse polymeric materials and maintain function of a wide variety of ribozymes. We participate in Penn State’s Astrobiology Research Center (ARC) in Chemical Origins of Life, and students can attain a dual degree in Chemistry and Astrobiology.Methods Applied
Group Members
Collaborators
Christine Keating (Penn State University)
Work is supported by NASA grant.
Representative Publications
- Poudyal, R. R., Meyer, M. O., Bevilacqua, P. C. Measuring the activity and structure of functional RNAs inside compartments formed by liquid-liquid phase separation. Methods Enzymol. (2021). [PubMed]
- Cakmak, F. P., Choi, S., Meyer, M. O., Bevilacqua, P. C., Keating, C. D. Prebiotically-relevant low polyion multivalency can improve functionality of membraneless compartments. Nature Commun. 11, 5949 (2020).
- Poudyal, R., Keating, C. D., Bevilacqua, P. C. Polyanion-assisted catalysis inside complex coacervates. ACS Chem. Biol. 14, 1243-1248 (2019). [PubMed] (link to 50 free e-prints).
- Poudyal, R.R., Guth, R.M., Veenis, A.J., Frankel, E.A., Keating, C.D., Bevilacqua, P.C. RNA functions inside membraneless compartments: Non-enzymatic RNA polymerization, small-molecule binding, and enhanced ribozyme catalysis. Nat. Commun. 10, 1-13 (2019) [PubMed] (open access).
- Frankel, E. A., Bevilacqua, P. C., Keating, C. D. “Polyamine/nucleotide coacervates provide strong compartmentalization of Mg2+, nucleotides, and RNA” Langmuir 32, 2041-2049 (2016). [PubMed]
- Dewey, D. C. Strulson, C. A., Cacace, D. N., Bevilacqua, P. C., and Keating, C. D. “Bioreactor droplets from liposome-stabilized all-aqueous emulsions.” Nature Comm. 5, 4670 (2014). [PubMed]
- Strulson, C. A., Molden, R. C., Keating, C. D., Bevilacqua, P. C. “RNA catalysis through compartmentalization” Nature Chemistry 4, 941-946 (2012).[Pubmed]
Review Articles
- Poudyal RR, Pir Cakmak F, Keating CD, Bevilacqua PC. Physical principles and extant biology reveal roles for RNA-containing membraneless compartments in origins of life chemistry. Biochemistry 57, 2509-2519 (2018) [PubMed]
- Frankel, E., Dewey, D., Keating, C. “Encapsulation of Organic Material in the Protocells.” Astrobiology, an Evolutionary Approach. Ed. Kolb, V.: CRC Press, 2014. Print.