title: Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication.
abstract: The non-enzymatic replication of RNA is thought to have been a critical process required for the origin of life. One unsolved difficulty with non-enzymatic RNA replication is that template-directed copying of RNA results in a double-stranded product. After strand separation, rapid strand reannealing outcompetes slow non-enzymatic template copying, which renders multiple rounds of RNA replication impossible. Here we show that oligoarginine peptides slow the annealing of complementary oligoribonucleotides by up to several thousand-fold; however, short primers and activated monomers can still bind to template strands, and template-directed primer extension can still occur, all within a phase-separated condensed state, or coacervate. Furthermore, we show that within this phase, partial template copying occurs even in the presence of full-length complementary strands. This method to enable further rounds of replication suggests one mechanism by which short non-coded peptides could have enhanced early cellular fitness, and potentially explains how longer coded peptides, that is, proteins, came to prominence in modern biology.
authors.affiliation: Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
authors.forename: Tony Z
authors.initials: TZ
authors.lastname: Jia
authors.affiliation: Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Earth-Life Science Institute, Tokyo Institute of Technology, 2-12-1-IE-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Fahrenbach
authors.affiliation: Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Neha P
authors.initials: NP
authors.lastname: Kamat
authors.affiliation: Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
authors.forename: Katarzyna P
authors.identifier: 0000-0003-1066-7207
authors.initials: KP
authors.lastname: Adamala
authors.affiliation: Department of Molecular Biology and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.|Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.|Earth-Life Science Institute, Tokyo Institute of Technology, 2-12-1-IE-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.|Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Szostak