# Cecilia Guerrier-Takada
**Cecilia Guerrier-Takada** was a molecular biologist who worked in [Sidney Altman](https://www.edgepedia.org/sidney-altman)'s laboratory at Yale University, first as a postdoctoral fellow and later as a senior research scientist. She was first author of the 1983 *Cell* paper demonstrating that the RNA moiety (A distinct part or component of a molecule) of ribonuclease P (RNase P) is the catalytic subunit of the enzyme, a central result in the discovery that RNA can act as a catalyst.[1](http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf) • [2](https://www.nobelprize.org/prizes/chemistry/1989/altman/article/) According to a 2024 *Journal of Biological Chemistry* article, the work underpinned Altman's share of the 1989 [Nobel Prize in Chemistry](https://www.edgepedia.org/nobel-prize-in-chemistry).[3](https://doi.org/10.1016/j.jbc.2024.107318)
| Key fact | Detail |
|---|---|
| Field | Molecular biology; RNA catalysis and RNase P[1](http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf) |
| Known for | Showing that the RNA subunit of RNase P is the enzyme's catalytic subunit (1983)[1](http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf) |
| Signature work | "The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme", *Cell*, 1983[1](http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf) |
| Affiliations | Yale University, Department of Biology, in Sidney Altman's laboratory[1](http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf) • [4](https://news.yale.edu/1997/08/04/yale-breakthrough-destroying-drug-resistant-bacteria-focuses-thwarting-genes-cause-resist) |
| Training | Postdoctoral fellow with Sidney Altman at Yale[2](https://www.nobelprize.org/prizes/chemistry/1989/altman/article/) |
| Later career | Senior research scientist at Yale (1997); external guide sequence technology against drug-resistant bacteria[4](https://news.yale.edu/1997/08/04/yale-breakthrough-destroying-drug-resistant-bacteria-focuses-thwarting-genes-cause-resist) |
| Last recorded work | "RNase P cleaves transient structures in some riboswitches", *PNAS*, 2005[5](https://www.rankless.org/authors/cecilia-guerriertakada) |
## Representative work
The 1983 *Cell* paper, with Guerrier-Takada as first author and Sidney Altman as senior author, showed that the RNA moieties of RNase P purified from *E. coli* (M1 RNA) and *B. subtilis* (P-RNA) cleave tRNA precursor molecules in buffers containing either 60 mM Mg2+ or 10 mM Mg2+ plus 1 mM spermidine. Under these conditions the RNA acts as a true catalyst, while the protein moieties alone show no catalytic activity. At lower magnesium concentrations (5–10 mM Mg2+, without spermidine) both subunits are required, and subunits from the two bacterial species can complement each other in reconstitution experiments.[1](http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf)
A companion experiment closed the obvious objection. M1 RNA produced by transcription of the gene in vitro performed the enzyme's cleavage reactions without any protein moiety, ruling out a contaminating protein as the catalyst; combined with the protein subunit, the transcript cleaved both a tRNA precursor and the precursor to *E. coli* 4.5S RNA.[6](https://doi.org/10.1126/science.6199841) According to a tribute to Altman in the journal *RNA*, the in vitro transcription experiment dates to a 1984 paper, while the corresponding *Science* paper is indexed with a 1983 DOI; the two records do not agree on the year.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9745839/) • [6](https://doi.org/10.1126/science.6199841)
Her 1986 *Cell* paper mapped which parts of M1 RNA are essential. Molecules missing as many as 122 nucleotides at the 3′ terminus retained catalytic activity, though at a much lower level than intact M1 RNA; no activity was observed with an RNA missing 70 nucleotides at the 5′ terminus, and removing even a small number of nucleotides from both termini eliminated all catalytic function.[8](https://articles.researchsolutions.com/m1-rna-with-large-terminal-deletions-retains-its-catalytic-activity/doi/10.1016/0092-8674(86)90381-8) In 1988 she showed, with colleagues, that M1 RNA alone and the RNase P holoenzyme cleave the tRNA-like structure of turnip yellow mosaic virus RNA in vitro at the 5′ side of the quasi-helical structure, and suggested that RNase P may have a second function in vivo in the physiology of viral infections.[9](https://articles.researchsolutions.com/novel-reactions-of-rnaase-p-with-a-trna-like-structure-in-turnip-yellow-mosaic-virus-rna/doi/10.1016/0092-8674(88)90388-1)
## Context: the discovery of RNA catalysis
The 1983 result overturned the lab's own earlier position. A 1978 paper from Altman's group had posited a supporting role for the RNA in RNase P; the 1983 paper demonstrated the RNA moiety as the catalytic subunit.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9745839/) The tribute to Altman credits Guerrier-Takada, described as an exceptional postdoctoral scientist, with finding in fall 1983, during reconstitution work, that each RNA subunit alone had catalytic activity in the presence of 60 mM Mg2+, a condition that had not previously been tested.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC9745839/) The Nobel Foundation's account states that she, as a postdoctoral fellow, demonstrated that the RNA itself was a true enzyme in vitro.[2](https://www.nobelprize.org/prizes/chemistry/1989/altman/article/)
Altman's Nobel Lecture records that M1 RNA had all the properties of a true enzyme: it was unchanged in size during the reaction, had a true turnover number by Michaelis-Menten analysis, and was needed in only small amounts and was stable.[10](https://www.nobelprize.org/uploads/2018/06/altman-lecture.pdf) A 2024 *Journal of Biological Chemistry* review frames the discovery as the basis for Altman's share of the 1989 Nobel Prize and as support for the RNA-world hypothesis, and notes that M1 RNA is a trans-acting, multiple-turnover catalyst, unlike the cis-acting group I intron; the term ribozyme was coined in connection with the self-splicing group I intron.[3](https://doi.org/10.1016/j.jbc.2024.107318)
## Later career: external guide sequences and antibacterial work
Guerrier-Takada spent the 1990s and early 2000s turning RNase P into a tool. In 1992 she showed that external guide sequences (EGSs), short RNAs as short as 13 nucleotides complementary to a target mRNA, direct specific cleavage by *E. coli* RNase P at sites predicted by the EGS sequence; DNA EGSs worked but about tenfold less efficiently than RNA EGSs.[11](https://doi.org/10.1073/pnas.89.8.3185) According to a 1995 study, plasmid-encoded EGSs reduced induced beta-galactosidase and alkaline phosphatase activity in *E. coli* by more than 50%, with no reduction from non-specific EGSs, and inhibition was abolished in strains temperature-sensitive for RNase P.[12](https://doi.org/10.1073/pnas.92.24.11115)
In August 1997 Yale announced that Altman, along with senior research scientist Cecilia Guerrier-Takada, had used techniques based on his Nobel-winning research to restore drug sensitivity to resistant bacteria. EGS molecules attach to a target mRNA and cause RNase P to destroy the bound mRNA, then are freed to repeat the process; in the study, drug sensitivity was restored in virtually all bacteria in laboratory test cultures, and the work was funded by the National Institute of General Medical Sciences.[4](https://news.yale.edu/1997/08/04/yale-breakthrough-destroying-drug-resistant-bacteria-focuses-thwarting-genes-cause-resist) The underlying 1997 *PNAS* paper, with Guerrier-Takada as first author, introduced plasmids carrying synthetic EGS genes into antibiotic-resistant *E. coli*, directing RNase P to cleave resistance-gene mRNAs and converting the cells' phenotype to drug sensitivity; increasing the EGS-to-target mRNA ratio enhanced the conversion.[13](https://doi.org/10.1073/pnas.94.16.8468) The EGS method was licensed exclusively to Innovir Laboratories, which had shown an EGS effective against hepatitis in animal experiments.[4](https://news.yale.edu/1997/08/04/yale-breakthrough-destroying-drug-resistant-bacteria-focuses-thwarting-genes-cause-resist) In 2002, EGSs targeting two essential genes, the C5 protein of RNase P and gyrase A, reduced microbial viability to less than 10% of the wild-type strain, demonstrating narrow-spectrum antibacterial activity.[14](https://doi.org/10.1073/pnas.121180398) Her last recorded work is a 2005 *PNAS* paper showing that RNase P cleaves transient structures in some riboswitches.[5](https://www.rankless.org/authors/cecilia-guerriertakada)
## Legacy
The 2024 *JBC* retrospective states that Guerrier-Takada and Altman conclusively showed that the catalytic activity resides in M1 RNA, using M1 RNA produced by in vitro SP6 RNA polymerase transcription.[3](https://doi.org/10.1016/j.jbc.2024.107318) Her own later experiments extended the finding: a 1992 *PNAS* paper showed that many fragments of M1 RNA can reassociate after simple mixing in vitro to form complexes with enzymatic activity typical of wild-type M1 RNA, and that two inactive M1 RNA molecules with nonoverlapping deletions can interact to form an active RNA enzyme.[15](https://doi.org/10.1073/pnas.89.4.1266) Altman's Nobel Lecture credits the general ionic requirements of the reaction to Guerrier-Takada et al. (1986).[10](https://www.nobelprize.org/uploads/2018/06/altman-lecture.pdf)
## References
1. Guerrier-Takada et al., "The RNA Moiety of Ribonuclease P Is the Catalytic Subunit of the Enzyme", *Cell* 35:849–857 (1983). http://dosequis.colorado.edu/courses/methodslogic/papers/Altman1983.pdf
2. "The RNA world", NobelPrize.org. https://www.nobelprize.org/prizes/chemistry/1989/altman/article/
3. "The discovery of a catalytic RNA within RNase P and its legacy", *Journal of Biological Chemistry* (2024). https://doi.org/10.1016/j.jbc.2024.107318
4. "Yale Breakthrough in Destroying Drug-Resistant Bacteria Focuses on Thwarting Genes that Cause Resistance", Yale News (1997). https://news.yale.edu/1997/08/04/yale-breakthrough-destroying-drug-resistant-bacteria-focuses-thwarting-genes-cause-resist
5. "Cecilia Guerrier-Takada", Rankless. https://www.rankless.org/authors/cecilia-guerriertakada
6. "Catalytic Activity of an RNA Molecule Prepared by Transcription in Vitro", *Science* (1983). https://doi.org/10.1126/science.6199841
7. "Tribute to Sidney Altman", *RNA* (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9745839/
8. https://articles.researchsolutions.com/m1-rna-with-large-terminal-deletions-retains-its-catalytic-activity/doi/10.1016/0092-8674(86)90381-8
9. https://articles.researchsolutions.com/novel-reactions-of-rnaase-p-with-a-trna-like-structure-in-turnip-yellow-mosaic-virus-rna/doi/10.1016/0092-8674(88)90388-1
10. Sidney Altman, Nobel Lecture (1990). https://www.nobelprize.org/uploads/2018/06/altman-lecture.pdf
11. "Targeted cleavage of mRNA in vitro by RNase P from Escherichia coli", *PNAS* (1992). https://doi.org/10.1073/pnas.89.8.3185
12. "Artificial regulation of gene expression in Escherichia coli by RNase P", *PNAS* (1995). https://doi.org/10.1073/pnas.92.24.11115
13. "Phenotypic conversion of drug-resistant bacteria to drug sensitivity", *PNAS* (1997). https://doi.org/10.1073/pnas.94.16.8468
14. "Inhibition of Escherichia coli viability by external guide sequences complementary to two essential genes", *PNAS* (2002). https://doi.org/10.1073/pnas.121180398
15. "Reconstitution of enzymatic activity from fragments of M1 RNA", *PNAS* (1992). https://doi.org/10.1073/pnas.89.4.1266
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in molecular and cell biology › RNA biology › Non-coding RNA and transcription*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026 · Last review: Sep 25, 2026*
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