The lost language of the RNA World

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Science Signaling  13 Jun 2017:
Vol. 10, Issue 483, eaam8812
DOI: 10.1126/scisignal.aam8812


  • Fig. 1 Biological ligands for the known natural riboswitch classes are predominantly derived from RNA.

    (A) Comprehensive list of ligands sensed by riboswitches, grouped according to general chemical types. (B) Chart depicting the total number of riboswitch classes organized according to their ligand types. Some compounds act as ligands for multiple riboswitch classes. For example, there are five distinct classes of riboswitches for S-adenosylmethionine: three for prequeuosine-1, two for 2′-deoxyguanosine, two for c-di-GMP, two for Mg2+, and three for guanidine.

  • Fig. 2 Known natural signaling compounds derived from RNA nucleotides or their precursors.

    The compound ppGpp, which carries a pyrophosphate both at the 5′ and 3′ positions, is derived from a pentaphosphate precursor (pppGpp) that carries a triphosphate on the 5′ position and is not shown. ZTP is AICA ribonucleoside 5′-triphosphate; AThTP is adenosine thiamine triphosphate. Asterisks denote putative signaling compounds for which biological roles and phylogenetic distributions have not been well established.

  • Fig. 3 The possible diversity of cyclic dinucleotide RNAs and their immediate degradation products.

    (A) Matrix depicting all 16 possible linear dinucleotides that can be directly generated by degradation of cyclic dinucleotide RNAs. Compounds are schematically represented by depicting the nucleoside (circled letter) joined by phosphate backbone atoms (p). Annotations i, a, b, c, and ia/b/c represent all possible combinations of isomers with variation in the phosphodiester linkage connectivity and variation in the location and connectivity of the terminal phosphate. (B) Matrix depicting all 10 possible cyclic dinucleotide RNAs formed by the four common ribonucleotides joined by 3′,5′-phosphodiester linkages. Annotations i, ii, and iii represent all possible combinations of derivatives wherein 2′,5′-phosphodiester linkages are present. The compounds for which there is evidence of biological roles in modern cells are highlighted in red.

  • Fig. 4 A complex all-RNA signal-receptor system.

    A natural allosteric ribozyme from Clostridium difficile uses a c-di-GMP-II riboswitch (21) to sense an RNA-based signaling molecule, whereupon ligand binding triggers proper self-splicing by a GTP-dependent group I ribozyme. Formation of the ribozyme P1 stem permits GTP (here designated GTP1) to attack the 5′ splice site (5′ SS). The newly formed 3′-hydroxyl group of G101 serves as a nucleophile to attack the 3′ splice site (3′ SS) that follows G667 of the ribozyme. Joining the exons creates a strong ribosome binding site that promotes translation of the adjacent open reading frame (ORF) (72). Without c-di-GMP, the riboswitch aptamer (boxed structure including the pseudoknot) and the ribozyme reorganize to permit the complementary regions highlighted in dark blue to base-pair, and the complementary regions shown in light blue to base-pair, which creates alternative stem P1*. This promotes GTP (here designated GTP2) to attack the riboswitch after G670, which precludes proper splicing. The resulting GTP2 attack product lacks nucleotides that otherwise could serve as a ribosome binding site, which prevents translation of the adjacent open reading frame. The solid line represents the RNA chain, with only specific nucleotides critical for the mechanism depicted. Dashed lines indicate zero-length connections.

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