A ribozyme transcribed by a ribozyme - PubMed (original) (raw)

A ribozyme transcribed by a ribozyme

Thomas Bentin. Artif DNA PNA XNA. 2011 Apr.

Abstract

Prominent current ideas on how life emerged on Earth include an RNA world hypothesis in which RNA performed informational as well as catalytic functions in the absence of both DNA and protein. Demonstration of a self-replicative system based on ribonucleic acid polymers as both information carriers and catalysts would lend support to such a scenario. A pivotal component of this system would be an RNA dependent RNA polymerase ribozyme capable of replicating its own RNA gene. Recent work from the Holliger group at the Laboratory for Molecular Biology in Cambridge has provided synthetic ribozymes1 that just might foreshadow the future engineering of such self-replicative systems.

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Figures

Figure 1

Figure 1

RNA polymerase ribozyme development, structure and characteristics. (A) ribozyme lineages showing the descent of tC19Z from R18. (B) Illustration of tC19Z bound via ssC19 to an RNA primer/template complex and active in primer extension (light blue). Brown, orange, green and purple nucleobases derives from R18, C19, tC19, and Z, respectively (same color code as in A). As regards the specific selected sequence elements, the ssC19-A4 combination facilitates template binding and RNA polymerase activity on longer templates; C60U provides a potential wobble base pair in the catalytic core (dashed line), and enhances RNA polymerase activity; G93A and G95A are compensatory mutations reducing a need for a short “stem” structure, which in R18 is provided by an RNA oligonucleotide in trans; A159C, located in the processivity domain, enables formation of the P12 stem by allowing G133:C159 base pairing. (C) Ribozyme characteristics. *The primer extension capability of tC19Z in terms of product length remains unknown because it was not tested with the long template yielding 95 nt products with tC19. **Template generality: according to Johnston et al. (2001), R18 worked with all primer/template complexes tested (producing RNA oligomers up to a maximum of 14 nt) and is therefore a general RNA polymerase. However, both R18 and tC19 remained template sequence dependent according to Wochner et al. (2011), and are therefore indicated as “limited” in the figure as opposed to tC19Z, which showed increased template sequence generality.

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References

    1. Wochner A, Attwater J, Coulson A, Holliger P. Ribozyme-catalyzed transcription of an active ribozyme. Science. 2011;332:209–212. -PubMed
    1. Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP. RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension. Science. 2001;292:1319–1325. -PubMed
    1. Nudler E. RNA polymerase active center: the molecular engine of transcription. Annu Rev Biochem. 2009;78:335–361. -PMC -PubMed

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