Michael Yarus

University of Colorado Boulder

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Rob Knight

University of California, San Diego

Irene Majerfeld

University of Colorado Boulder

Mali Illangasekare

University of Colorado Boulder

Steven W. Cline

Dalhousie University

Linda Breeden

Fred Hutch Cancer Center

Teresa Janas

University of Opole

Faqing Huang

University of Southern Mississippi

Larry Soll

University of Colorado Boulder

Tadeusz Janas

University of Opole

James F. Curran

Wake Forest University

Cooperative Institutions

University of Colorado Boulder

Howard Hughes Medical Institute

University of Colorado System

Centre National de la Recherche Scientifique

University of California, San Diego

University of Wisconsin–Madison

Stanford University

Harvard University

Cornell University

University of California, San Francisco

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Tests of a Stereochemical Genetic Code

Rob Knight Laura F. Landweber Michael Yarus

Code (set theory)

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Citations (8)

The u.v.-resistance of double-stranded φX174 DNA

Journal of Molecular Biology (1964)

Michael Yarus Robert L. Sinsheimer

Pyrimidine dimer

Double stranded

10.1016/s0022-2836(64)80018-8

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Citations (58)

Aminoacyl-RNA Synthesis Catalyzed by an RNA

Science (1995)

Mali Illangasekare Giselle Sánchez Tim Nickles Michael Yarus

An RNA has been selected that rapidly aminoacylates its 2′(3′) terminus when provided with phenylalanyl-adenosine monophosphate. That is, the RNA accelerates the same aminoacyl group transfer catalyzed by protein aminoacyl-transfer RNA synthetases. The best characterized RNA reaction requires both Mg 2+ and Ca 2+ . These results confirm a necessary prediction of the RNA world hypothesis and represent efficient RNA reaction (≥ 10 5 times accelerated) at a carbonyl carbon, exemplifying a little explored type of RNA catalysis.

10.1126/science.7530860

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Citations (349)

RNA enzymes with two small-molecule substrates

Chemistry & Biology (1998)

Faqing Huang Zhili Yang Michael Yarus

Ligase ribozyme

Riboswitch

10.1016/s1074-5521(98)90294-0

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Citations (33)

Multiple translational products from a five-nucleotide ribozyme

Proceedings of the National Academy of Sciences (2010)

Rebecca M. Turk Nataliya Chumachenko Michael Yarus

An indispensable step in protein biosynthesis is the 2 ′ (3 ′ ) aminoacylation of tRNA by aminoacyl-tRNA synthetases. Here we show that a similar activity exists in a tiny, 5-nt-long RNA enzyme with a 3-nt active center. The small ribozyme initially trans -phenylalanylates a partially complementary 4-nt RNA selectively at its terminal 2 ′ -ribose hydroxyl using PheAMP, the natural form for activated amino acid. The initial 2 ′ Phe-RNA product can be elaborated into multiple peptidyl-RNAs. Reactions do not require divalent cations, and have limited dependence on monovalent cations. Small size and minimal requirements for regiospecific translational activity strongly support the hypothesis that minuscule RNA enzymes participated in early forms of translation.

Aminoacylation

Ligase ribozyme

VS ribozyme

Ribose

Divalent

Amino Acyl-tRNA Synthetases

10.1073/pnas.0912895107

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Citations (149)

The Plausibility of RNA-Templated Peptides: Simultaneous RNA Affinity for Adjacent Peptide Side Chains

Journal of Molecular Evolution (2012)

Rebecca Turk-MacLeod Deepa Puthenvedu Irene Majerfeld Michael Yarus

According to the RNA world hypothesis, coded peptide synthesis (translation) must have been first catalyzed by RNAs. Here, we show that small RNA sequences can simultaneously bind the dissimilar amino acids His and Phe in peptide linkage. We used in vitro counterselection/selection to isolate a pool of RNAs that bind the dipeptide NH2-His-Phe-COOH with K D ranging from 36 to 480 μM. These sites contact both side chains, usually including the protonated imidazole of His, but bind-free l-His and l-Phe with much lower, sometimes undetectable, affinities. The most frequent His–Phe sites do not usually contain previously isolated sites for individual amino acids, and are only ≈35 % larger than previously known separate His and Phe sites. Nonetheless, His–Phe sites appear enriched in His anticodons, as previous l-His sites also were. Accordingly, these data add to existing experimental evidence for a stereochemical genetic code. In these peptide sites, bound amino acids approach each other to a proximity that allows a covalent peptide linkage. Isolation of several RNAs embracing two amino acids with a linking peptide bond supports the idea that a direct-RNA-template could encode primordial peptides, though crucial experiments remain.

Genetic Code

10.1007/s00239-012-9501-8

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Citations (18)

Faculty Opinions recommendation of The evolution and functional repertoire of translation proteins following the origin of life.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2010)

Michael Yarus

BACKGROUND: The RNA world hypothesis posits that the earliest genetic system consisted of informational RNA molecules that directed the synthesis of modestly functional RNA molecules. Further evidence suggests that it was within this RNA-based genetic system that life developed the ability to synthesize proteins by translating genetic code. Here we investigate the early development of the translation system through an evolutionary survey of protein architectures associated with modern translation.RESULTS: Our analysis reveals a structural expansion of translation proteins immediately following the RNA world and well before the establishment of the DNA genome. Subsequent functional annotation shows that representatives of the ten most ancestral protein architectures are responsible for all of the core protein functions found in modern translation.CONCLUSIONS: We propose that this early robust translation system evolved by virtue of a positive feedback cycle in which the system was able to create increasingly complex proteins to further enhance its own function. PMID: 20377891 Funding information This work was supported by: NLM NIH HHS, United States Grant ID: DP1 LM011509

Genetic Code

RNA world hypothesis

10.3410/f.4805956.4715054

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Citations (0)

The Translational Context Effect

CRC Press eBooks (2018)

Michael Yarus James F. Curran

A protein can be encoded by a prodigious number of nucleotide sequences. A context effect is a functional interaction between distinct sites in messenger ribonucleic acid (mRNA); namely, a codon and its neighboring nucleotides. Context may have immediate translational effects; on the frequency of missense, frameshift, and chain loss errors. Context may also be subtle, triggering a chain of events that ultimately affect expression by another route. For example, differences in translational rate alter ribosomal distribution, which may conceivably lead to effects on mRNA synthesis and decay. It follows easily that if nucleotide context differentially affects transfer ribonucleic acid (tRNA) selection, it will affect the mistaken substitution of one tRNA for another. There is evidence for context effects on missense error frequencies. Relatively unperturbed tRNA-tRNA interfaces differ roughly 9-fold in the rate of tRNA selection they permit.

10.1201/9781351077392-11

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Citations (3)

[Interaction of RNA with phospholipid membranes].

Molecular Biology (2002)

Alexander V. Vlassov Michael Yarus

RNA world hypothesis

10.1023/a:1016063414162

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Citations (13)

Optimal Evolution of the Standard Genetic Code

Journal of Molecular Evolution (2021)

Michael Yarus

Abstract The Standard Genetic Code (SGC) exists in every known organism on Earth. SGC evolution via early unique codon assignment, then later wobble, yields coding resembling the near-universal code. Below, later wobble is shown to also create an optimal route to accurate codon assignment. Time of optimal codon assignment matches the previously defined mean time for ordered coding, exhibiting ≥ 90% of SGC order. Accurate evolution is also accessible, sufficiently frequent to appear in populations of 10 3 to 10 4 codes. SGC-like coding capacity, code order, and accurate assignments therefore arise together, in one attainable evolutionary intermediate. Examples, which plausibly resemble coding at evolutionary domain separation, are characterized.

Genetic Code

Speed wobble

Code (set theory)

Coding region

10.1007/s00239-020-09984-8

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Citations (14)