An element within the 5′ untranslated region of human Hsp70 mRNA which acts as a general enhancer of mRNA translation
Open accessAbstract
The untranslated regions of mRNAs encoding heat‐shock proteins have been reported to contain elements important to the post‐transcriptional regulation of these key components of the stress response. In this report we describe an element from the 5′UTR of human Hsp70 mRNA that increases the efficiency of mRNA translation. Cloning of this region upstream of the coding sequence of two different reporter genes (firefly luciferase and chloramphenicol acetyltransferase) increases expression of the reporter under normal cell culture conditions by up to an order of magnitude. This effect was observed in three different promoter contexts (HSP, SV40 and CMV) and in six cell lines. The increase in protein production is not accompanied by any alteration in mRNA levels, suggesting that the element facilitates translation. 5′ or 3′ truncated sequences are ineffective in enhancing reporter expression, suggesting that the activity arises from the secondary structure of the element, rather than from some smaller defined motif. Computer analysis of this region revealed that it is able to form stable secondary structures (Δ G ≈ −292.6 kJ·mol−1). The Hsp70 element does not seem to act as an internal ribosome entry site. Incorporation of the sequence into plasmids used for DNA vaccination produces increased antibody responses, confirming that the sequence is functional in primary cells. These data suggest that the 5′UTR of human Hsp70 mRNA plays an important role in determining Hsp70 expression levels, and that it contains an element of general utility in enhancing recombinant protein expression systems.
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The Hsp70 5′ UTR has an enhancer element and can promote translation via both cap-dependent and cap-independent mechanisms.
“The higher expression of Hsp70 5′ UTR-mRNA in DC 2.4 may be attributed to an enhancer element in its sequence and to its capability to promote translation via both cap-dependent and cap-independent mechanisms.26,31”
From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [26]
The Abstract identifies a human Hsp70 5′ UTR element that enhances translation, and the Discussion says it improves translation during cap-dependent protein synthesis. The section “The Hsp70 5′ UTR does not behave as an IRES” reports no IRES activity; the Discussion leaves translation when cap-dependent synthesis is downregulated as an open question. This paper therefore does not support the cap-independent part of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe human Hsp70 5′ UTR is reported to be a general enhancer of mRNA translation.
“the human Hsp70 5′ UTR reported to be a general enhancer of mRNA translation26”
From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [26]
The effect of HSP70 5′UTR has been observed in several cell lines, indicating that this effect is not cell type specific.
“The effect of HSP70 5′UTR has been observed in several cell lines [14], indicating that this effect is not cell type specific.”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [14]
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Cites
CpG motifs in bacterial DNA trigger direct B-cell activation
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- Rabindran, S.K., Giorgi, G., Clos, J. & Wu, C. (1991) Molecular cloning and expression of a human heat shock factor, HSF1. Proc. Natl Acad. Sci. USA 88, 6906±6910.
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Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J. (2012) · RNA Biology · doi:10.4161/rna.22269 · Cited by 622 · see citing works
New Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579 · see citing works
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Minnaert, A.-K., Vanluchene, H., Verbeke, R., Lentacker, I., De Smedt, S. C., Raemdonck, K., Sanders, N. N., & Remaut, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113900 · Cited by 157 · see citing works
Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis
Reshetnikov, V., Terenin, I., Shepelkova, G., Yeremeev, V., Kolmykov, S., Nagornykh, M., Kolosova, E., Sokolova, T., Zaborova, O., Kukushkin, I., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020888 · Cited by 33 · see citing works
Medjmedj, A., Genon, H., Hezili, D., Loth, A. N., Clemençon, R., Guimpied, C., Mollet, L., Bigot, A., Wien, F., Hamacek, J., et al. (2025) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2025.102648 · Cited by 19 · see citing works
- Authors
- Vivinus, S., Baulande, S., van Zanten, M., Campbell, F., Topley, P., Ellis, J. H., Dessen, P., & Coste, H.
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 2001-04
- Volume
- 268
- Issue
- 7
- Pages
- 1908-1917
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W1484915017
- Cited by
- 67
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 3 · 2018: 5 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- HSP70, 5' untranslated region, heat shock proteins, post-transcriptional regulation, RNA secondary structure, internal ribosome entry site, DNA vaccine, antibody response, recombinant protein expression, reporter gene expression
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Antigens, Polyomavirus Transforming, Carrier Proteins, Cell Line, Heat-Shock Proteins, Humans, Luciferases, Lymphokines, Nucleic Acid Conformation, Promoter Regions, Genetic, RNA, Messenger, Protein Biosynthesis, Chloramphenicol O-Acetyltransferase, Endothelial Growth Factors, Genes, Reporter, Molecular Chaperones, HSP70 Heat-Shock Proteins, Vaccines, DNA, 5' Untranslated Regions, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
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