# Karen U. Sprague
Karen U. Sprague is a molecular biologist known for her work on the tRNA genes and fibroin gene of the silkworm *Bombyx mori*, which she used to show how sequences flanking a gene control its transcription. She spent her research career at the [University of Oregon](https://www.edgepedia.org/university-of-oregon) in Eugene, where she is now Professor Emerita of Biology, and her laboratory studied the regulation of gene expression in the silk gland.
| Key fact | Detail |
|---|---|
| Field | Molecular biology; regulation of gene expression |
| Training | BA, Bryn Mawr, 1964; PhD, Yale, 1970 [1](https://catalog.uoregon.edu/arts-sciences/natural-sciences/biology/) |
| Career | University of Oregon from 1977; Professor Emerita, Biology [1](https://catalog.uoregon.edu/arts-sciences/natural-sciences/biology/) • [2](https://cas.uoregon.edu/directory/biology/all/kus) |
| Signature work | "5′ flanking sequence signals are required for activity of silkworm alanine tRNA genes in homologous in vitro transcription systems", *Cell*, 1980 [3](https://doi.org/10.1016/0092-8674(80)90165-8) |
| Main funding | NIH R01 GM025388 (NIGMS), 1978–1994; NIH K04 Career Development Award (NICHD), 1981–1986 [4](https://grantome.com/grant/NIH/R01-GM025388-15) • [5](https://grantome.com/index.php/grant/NIH/K04-HD000420-05) |
| Research system | *Bombyx mori* posterior silk gland and its alanine tRNA and fibroin genes [6](https://staging.europepmc.org/article/MED/884735) |
| Status (2026) | Professor Emerita; laboratory inactive [2](https://cas.uoregon.edu/directory/biology/all/kus) |
## Education and career
Sprague earned her bachelor's degree at [Bryn Mawr College](https://www.edgepedia.org/bryn-mawr-college) in 1964 and her doctorate at Yale University in 1970. According to a 1979 paper in *Cell*, she joined the University of Oregon in 1977, where her later papers list her at the Institute of Molecular Biology in Eugene. [1](https://catalog.uoregon.edu/arts-sciences/natural-sciences/biology/) • [7](https://www.cell.com/cell/abstract/0092-8674(79)90167-3) The University of Oregon catalog records her appointment year as 1977; her current title is professor emerita, and the directory does not give a retirement year. [2](https://cas.uoregon.edu/directory/biology/all/kus)
## Representative work
Her 1980 *Cell* paper, 5′ flanking sequence signals are required for activity of silkworm alanine tRNA genes in homologous in vitro transcription systems, showed that DNA outside the coding sequence of a tRNA gene is needed for that gene to be transcribed. [3](https://doi.org/10.1016/0092-8674(80)90165-8) This mattered because tRNA genes are read by [RNA polymerase III](https://www.edgepedia.org/rna-polymerase-iii), an enzyme class whose control regions were then being mapped inside genes; the paper established that in the silkworm's own transcription system, upstream DNA carries required signals as well. [3](https://doi.org/10.1016/0092-8674(80)90165-8) • [8](https://doi.org/10.1093/nar/10.18.5393)
Three companion papers framed that result. The 1977 *Cell* paper determined the nucleotide sequences of the two major alanine tRNAs of the *Bombyx mori* posterior silk gland, one of which appears specific to the silk gland, where its accumulation accompanies rapid fibroin production; the two sequences differ by a single nucleotide in the anticodon stem, and both carry loop IV sequences previously believed restricted to initiator tRNA. [6](https://staging.europepmc.org/article/MED/884735) A 1979 *Cell* paper analyzed silkworms producing fibroin proteins of different lengths and showed they possess variant alleles of a single fibroin gene, concluding that rearrangements within the gene's highly repetitive sequences arise by unequal recombination and can alter coding length. [7](https://www.cell.com/cell/abstract/0092-8674(79)90167-3) A second 1979 *Cell* paper identified the in vitro sites of initiation, termination, and processing of a silkworm alanine tRNA gene's primary transcript. [9](https://doi.org/10.1016/0092-8674(79)90234-4)
## Research program and system
The silkworm silk gland offered a natural experiment in gene control. [Silk fibroin](https://www.edgepedia.org/silk-fibroin), at 29 percent alanine, 46 percent glycine, and 12 percent serine, is synthesized exclusively in the posterior part of the gland, and one alanine tRNA species is found only there, accumulating at a high level during the fibroin secretion phase. [10](https://doi.org/10.1016/0014-5793(77)80246-9) One *Bombyx* alanine tRNA is constitutive, present in many cell types, while the other appears only in the silk gland, predominating when that tissue makes large amounts of the alanine-rich fibroin. [11](https://doi.org/10.1017/s0424820100098885) A single tissue with two nearly identical genes expressed differently gave the laboratory a clean system for asking what switches a gene on.
Over the following decade the lab dissected those switches. A 1982 study found that silkworm 5S RNA and tRNA2Ala genes share conserved oligonucleotides located 29, 19, and 3 nucleotides before their transcription initiation sites. [12](https://doi.org/10.1128/mcb.2.12.1524-1531.1982) A 1983 PNAS study, using partially deleted genes, identified an upstream control signal required for transcription of a tRNA2Ala gene, with the 5′ boundary of the essential region lying between 34 and 11 nucleotides before the initiation site, and found oligonucleotides conserved among several *Bombyx* RNA polymerase III genes, suggesting a general control function. [13](https://doi.org/10.1073/pnas.80.11.3416) In 1986 the lab showed that the distinctive transcriptional properties of constitutive and silk gland-specific tRNAAla genes result from different positive signals upstream of their initiation sites. [14](https://doi.org/10.1073/pnas.83.2.374) A 1993 *Nucleic Acids Research* paper showed that two AT-rich upstream elements, with consensus sequences TATAT and AATTTT centered at about −30 and −20, direct transcription of a silkworm \(tRNA^{\mathrm{CAla}}\) gene; surveying 282 tRNA genes from 20 species, it found AT-rich upstream sequences in every group except vertebrates. [15](https://doi.org/10.1093/nar/21.25.5875)
[4](https://grantome.com/grant/NIH/R01-GM025388-15)
## How the approach compared
The upstream-signal question was being answered in parallel in other organisms by other methods. A 1982 *Nucleic Acids Research* study of a *Drosophila* tRNA minigene showed that the intragenic control regions alone could initiate transcription in *Xenopus* and HeLa systems, but that deleting 5′ flanking sequences had its most pronounced effect in the *Drosophila* transcription system. [8](https://doi.org/10.1093/nar/10.18.5393) Sprague's 1980 result made the same point more directly by working in a homologous silkworm system, where the flanking requirement could be seen without cross-species complications. [3](https://doi.org/10.1016/0092-8674(80)90165-8)
## Honors, funding, and roles
Her NIH research project on control of tRNA gene expression in *Bombyx mori* ran from 1 August 1978 to 31 July 1994 at the University of Oregon, supported by the National Institute of General Medical Sciences through R01 GM025388. [4](https://grantome.com/grant/NIH/R01-GM025388-15) She also held a Research Career Development Award (K04 HD000420) from the Eunice Kennedy Shriver National Institute of Child Health and [Human Development](https://www.edgepedia.org/human-development) from 1 July 1981 to 30 June 1986. [5](https://grantome.com/index.php/grant/NIH/K04-HD000420-05) The 1986 PNAS study was funded by NIGMS and NICHD. [14](https://doi.org/10.1073/pnas.83.2.374)
## Current status
As of the University of Oregon directory, Sprague is listed as Professor Emerita in Biology, with a listed research area of Cell and Developmental Biology, the research topic [Regulation of gene expression](https://www.edgepedia.org/regulation-of-gene-expression), and a laboratory marked inactive. [2](https://cas.uoregon.edu/directory/biology/all/kus)
## References
1. Biology | University of Oregon Academic Catalog. https://catalog.uoregon.edu/arts-sciences/natural-sciences/biology/
2. Karen Sprague | College of Arts and Sciences, University of Oregon. https://cas.uoregon.edu/directory/biology/all/kus
3. https://doi.org/10.1016/0092-8674(80)90165-8
4. Control of tRNA Gene Expression in *Bombyx mori* (NIH R01 GM025388-15 grant record). https://grantome.com/grant/NIH/R01-GM025388-15
5. Control of tRNA Gene Expression in *Bombyx mori* (NIH K04 HD000420-05 grant record). https://grantome.com/index.php/grant/NIH/K04-HD000420-05
6. The nucleotide sequence of two silk gland alanine tRNAs (Europe PMC abstract). https://staging.europepmc.org/article/MED/884735
7. https://www.cell.com/cell/abstract/0092-8674(79)90167-3
8. The minimum intragenic sequences required for promotion of eukaryotic tRNA gene transcription. *Nucleic Acids Research*, 1982. https://doi.org/10.1093/nar/10.18.5393
9. https://doi.org/10.1016/0092-8674(79)90234-4
10. https://doi.org/10.1016/0014-5793(77)80246-9
11. Control of Transcription of tRNA Genes. Proceedings annual meeting Electron Microscopy Society of America, 1981. https://doi.org/10.1017/s0424820100098885
12. Silkworm 5S RNA and Alanine tRNA Genes Share Highly Conserved 5′ Flanking and Coding Sequences. *Molecular and Cellular Biology*, 1982. https://doi.org/10.1128/mcb.2.12.1524-1531.1982
13. A short 5′ flanking region containing conserved sequences is required for silkworm alanine tRNA gene activity. *PNAS*, 1983. https://doi.org/10.1073/pnas.80.11.3416
14. Upstream sequences confer distinctive transcriptional properties on genes encoding silkgland-specific tRNAAla. *PNAS*, 1986. https://doi.org/10.1073/pnas.83.2.374
15. Transcription of a silkworm tRNA^CAla gene is directed by two AT-rich upstream sequence elements. *Nucleic Acids Research*, 1993. https://doi.org/10.1093/nar/21.25.5875
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in molecular and cell biology › RNA biology*
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