The Ribosome Functions as a Ribozyme

Lilley, David M.J.

doi:10.1002/1439-7633(20010105)2:1<31::aid-cbic31>3.0.co;2-p

Cited by 31 publications

(7 citation statements)

References 25 publications

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“…The 40S subunit decodes the genetic information carried on an mRNA transcript and the larger 60S subunit catalyses the formation of peptide bond. Ribosomes are also known as ‘ribozymes’, as the decoding and peptidyl transferase functions are carried out by the non-coding RNAs (ncRNAs) they harbour (13,14). The 18S and 25S rRNA of small and large subunits has been reported to undergo different chemical modifications to optimize their role in translation of genetic information, which demands high fidelity and structural complexity.…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae

Sharma

Watzinger

Kötter

et al. 2013

Nucleic Acids Research

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The 25S rRNA of yeast contains several base modifications in the functionally important regions. The enzymes responsible for most of these base modifications remained unknown. Recently, we identified Rrp8 as a methyltransferase involved in m1A645 modification of 25S rRNA. Here, we discovered a previously uncharacterized gene YBR141C to be responsible for second m1A2142 modification of helix 65 of 25S rRNA. The gene was identified by reversed phase–HPLC screening of all deletion mutants of putative RNA methyltransferase and was confirmed by gene complementation and phenotypic characterization. Because of the function of its encoded protein, YBR141C was named BMT2 (base methyltransferase of 25S RNA). Helix 65 belongs to domain IV, which accounts for most of the intersubunit surface of the large subunit. The 3D structure prediction of Bmt2 supported it to be an Ado Met methyltransferase belonging to Rossmann fold superfamily. In addition, we demonstrated that the substitution of G180R in the S-adenosyl-l-methionine–binding motif drastically reduces the catalytic function of the protein in vivo. Furthermore, we analysed the significance of m1A2142 modification in ribosome synthesis and translation. Intriguingly, the loss of m1A2142 modification confers anisomycin and peroxide sensitivity to the cells. Our results underline the importance of RNA modifications in cellular physiology.

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Section: Introductionmentioning

confidence: 99%

Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae

Sharma

Watzinger

Kötter

et al. 2013

Nucleic Acids Research

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“…Structural and functional analyses of ribosomes have revealed that it is the rRNA that makes the structural framework of ribosomes and catalyze the joining of amino acids (peptidyl transfer) during translation, hence making ribosome a ribozyme (1,2). However, the chemical composition of RNA, on the other hand, seems to be rather insufficient to provide the structural complexity and flexibility that RNA requires to catalyze the chemical reactions and coordinate the molecular events during protein synthesis.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m3U methylations of 25S rRNA in Saccharomyces cerevisiae

Sharma

Yang

Düttmann

et al. 2013

Nucleic Acids Research

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RNA contains various chemical modifications that expand its otherwise limited repertoire to mediate complex processes like translation and gene regulation. 25S rRNA of the large subunit of ribosome contains eight base methylations. Except for the methylation of uridine residues, methyltransferases for all other known base methylations have been recently identified. Here we report the identification of BMT5 (YIL096C) and BMT6 (YLR063W), two previously uncharacterized genes, to be responsible for m3U2634 and m3U2843 methylation of the 25S rRNA, respectively. These genes were identified by RP-HPLC screening of all deletion mutants of putative RNA methyltransferases and were confirmed by gene complementation and phenotypic characterization. Both proteins belong to Rossmann-fold–like methyltransferases and the point mutations in the S-adenosyl-l-methionine binding pocket abolish the methylation reaction. Bmt5 localizes in the nucleolus, whereas Bmt6 is localized predominantly in the cytoplasm. Furthermore, we showed that 25S rRNA of yeast does not contain any m5U residues as previously predicted. With Bmt5 and Bmt6, all base methyltransferases of the 25S rRNA have been identified. This will facilitate the analyses of the significance of these modifications in ribosome function and cellular physiology.

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“…The docked state, also called the pre-catalytic state being necessary for the catalytic step to take place, is formed by a rearrangement of loops A and B (Fig. 1b) by coming into close vicinity252627. Importantly, it has been found that the neighbouring nucleobases A38 and G8 in the reaction site have important roles in stabilizing the transition state via distinct hydrogen bonding interactions2829303132.…”

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confidence: 99%

Pressure modulates the self-cleavage step of the hairpin ribozyme

et al. 2017

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The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties.

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The Ribosome Functions as a Ribozyme

Cited by 31 publications

References 25 publications

Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae

Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae

Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m3U methylations of 25S rRNA in Saccharomyces cerevisiae

Pressure modulates the self-cleavage step of the hairpin ribozyme

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