RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer

David M.J. Lilley; Lin Huang

doi:10.1016/j.tibs.2025.01.011

RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer

David M.J. Lilley (Lead / Corresponding author)
, Lin Huang (Lead / Corresponding author)

Molecular Cell and Developmental Biology

Research output: Contribution to journal › Review article › peer-review

3 Citations (Scopus)

7 Downloads (Pure)

Abstract

The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.

Original language	English
Pages (from-to)	417-424
Number of pages	8
Journal	Trends in Biochemical Sciences
Volume	50
Issue number	5
Early online date	7 Mar 2025
DOIs	https://doi.org/10.1016/j.tibs.2025.01.011
Publication status	Published - May 2025

Keywords

alkyl transfer reactions
catalytic mechanisms
general acid catalysis
ribozymes
the RNA world hypothesis

ASJC Scopus subject areas

Biochemistry
Molecular Biology

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10.1016/j.tibs.2025.01.011

Author Accepted ManuscriptAccepted author manuscript, 338 KBLicence: CC BY-NC-ND

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title = "RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer",

abstract = "The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.",

keywords = "alkyl transfer reactions, catalytic mechanisms, general acid catalysis, ribozymes, the RNA world hypothesis",

author = "Lilley, \{David M.J.\} and Lin Huang",

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T1 - RNA catalysis moving towards metabolic reactions

T2 - progress with ribozyme catalyzed alkyl transfer

AU - Lilley, David M.J.

AU - Huang, Lin

PY - 2025/5

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N2 - The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.

AB - The RNA world hypothesis proposes that the early stages of the emergence of life on Earth comprised primitive cells in which RNA acted both to store genetic information and catalyze chemical reactions as RNA enzymes (ribozymes). Most contemporary ribozymes catalyze phosphoryl transfer reactions, but early ribozymes would have been required to catalyze a broader range of metabolic interconversions. None has been found in modern cells, yet ribozymes have been generated by in vitro evolution to catalyze several different chemical reactions, providing proof of principle of RNA-catalyzed metabolism. Recently, several different ribozymes that accelerate methyl or alkyl transfer have been isolated. As we discuss here, one of these, MTR1, uses a remarkably sophisticated catalytic mechanism involving nucleobase-mediated general acid catalysis.

KW - alkyl transfer reactions

KW - catalytic mechanisms

KW - general acid catalysis

KW - ribozymes

KW - the RNA world hypothesis

U2 - 10.1016/j.tibs.2025.01.011

DO - 10.1016/j.tibs.2025.01.011

M3 - Review article

C2 - 40055123

AN - SCOPUS:86000370023

SN - 0968-0004

VL - 50

SP - 417

EP - 424

JO - Trends in Biochemical Sciences

JF - Trends in Biochemical Sciences

IS - 5

ER -

RNA catalysis moving towards metabolic reactions: progress with ribozyme catalyzed alkyl transfer

Abstract

Keywords

ASJC Scopus subject areas

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