Globin gene transcripts can utilize histone gene 3′ end processing signals
Open accessAbstract
Deletion of the poly(A) site from the human alpha globin gene results in a defective gene that produces very little stable mRNA as compared to the intact gene, presumably due to the instability of the mRNA. However, if the Alpha poly(A) site is replaced by mouse histone H4 3' end processing signals, significant levels of hybrid alpha/H4 mRNA are obtained and the transcripts formed are cytoplasmic and poly(A)-. When both mouse histone 3' end processing signals and the alpha globin poly(A) site signals are placed in tandem after the alpha globin gene promoter and coding sequence, the alpha poly(A) site signals are utilized exclusively. These results show that the histone 3' end processing signals can function independently of the histone promoter and the transcripts which are normally polyadenylated (alpha globin) can be stabilized by a poly(A)- histone mRNA 3' terminus. Furthermore, these results show that the histone 3' end processing signals are less efficient than the alpha globin poly(A) site signals, if the two are placed in direct competition.
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Deleting the poly(A) region from mRNA results in mRNA being unstable compared to the intact gene.
“Deleting the poly(A) region from mRNA results in mRNA being unstable compared to the intact gene (Whitelaw et al. 1986).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Whitelaw et al. 1986
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Research works printed but not linked: 2
- RU-EKENCES L Lewin B., Genes II, Wiley & Son, 1985 2. Darnell J.E., Nature 297, 365-371 (1982)
- Luscher B., Stauber C, Schindler R. and Schumperli D., Proc.Natl.Acad.Sci. USA 82, 4389 (1985)
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Kim, S. C., Sekhon, S. S., Shin, W.-R., Ahn, G., Cho, B.-K., Ahn, J.-Y., & Kim, Y.-H. (2022) · Molecular & Cellular Toxicology · doi:10.1007/s13273-021-00171-4 · Cited by 255 · see citing works
Wu, Z., Sun, J., Zhang, T., Yin, C., Yin, F., Van Dyke, T., Samulski, R. J., & Monahan, P. E. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300355 · Cited by 153 · see citing works
- Authors
- Whitelaw, E., Coates, A., & Proudfoot, N. J.
- Affiliations
- University of Oxford (GB)
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1986
- Volume
- 14
- Issue
- 17
- Pages
- 7059-7070
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC311717
- OpenAlex
- W1969445988
- Cited by
- 17
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2021: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- globin genes, alpha-globin, polyadenylation, poly(A) site, histone H4, mRNA stability, poly(A)
- MeSH terms
- Animals, Gene Expression Regulation, Genetic Engineering, Globins, HeLa Cells, Histones, Humans, Poly A, RNA Processing, Post-Transcriptional, RNA, Messenger, Mice
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