Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations

Abstract

The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.

Synthesis and Incorporation of k2U into RNA

“…They directly merge the properties of nucleic acids with those of amino acids. As such, RNA containing these amino acid‐modified bases could have been a central element for the origin of life and for the origin of translation as already discussed by Grosjean and others . RNA containing these amino acids could establish catalytic properties next to information encoding functions.…”

The Simplest, Isolable, Alkynyl Isocyanate HC≡CNCO: Synthesis and Characterization

“…In particular, the prototype molecules such as HNCO and CH 3 NCO have been shown to be products of various forms of combustion such as biomass burning, cooking, and cigarette smoking, and they are also interstellar species that have been detected in Sgr B2(N), the hot core of a giant molecular cloud near the galactic center . Therefore, the structures and reactivity of isocyanates such as HNCO and CH 3 NCO have been the focus of numerous experimental and theoretical studies.…”

Advances in the Synthesis of Methylated Products through Indirect Approaches

“…In general, N‐methylation through the reduction of N,S‐linked methylene intermediates has not been widely applied, presumably because of the unpleasant odour of thiols. Nevertheless, the two recent examples in Table show that both NaBH 4 and an Na/NH 3 system work well.…”