Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection
Open accessAbstract
A series of adenovirus type 5 variants was constructed to probe the function of the tripartite leader sequence, a 200-nucleotide, 5' noncoding sequence carried on the majority of late viral mRNAs. Recombinant plasmids were constructed that carried the major late transcriptional control region followed by portions of the tripartite leader sequence fused to the E1A coding region. These modified E1A genes were then rebuilt into intact viral chromosomes, replacing the corresponding wild-type region. The leader segments had no effect on the translation of E1A mRNAs early after infection, but the tripartite leader significantly enhanced (5-fold) the efficiency with which the mRNAs were translated late after infection.
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TPL is a nucleotide sequence in the 5′UTR of adenovirus late mRNAs and has previously been thought to initiate translation of late adenoviral mRNAs in a cap-independent manner.
“TPL is a nucleotide sequence in the 5′UTR of adenovirus late mRNAs and has previously been thought to initiate translation of late adenoviral mRNAs in a cap-independent manner [15,36].”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [36]
The paper’s introductory passage identifies the tripartite leader as a 5′ nontranslated sequence shared by most late adenoviral mRNAs. The Discussion says it likely plays a role in translation initiation, but does not say that initiation is cap-independent; that mechanism is unsupported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTPL contains an internal ribosome entry site enabling it to recruit a ribosome independently of interactions with the mRNA 5′ 7-methyl G cap.
“TPL contains an internal ribosome entry site enabling it to recruit a ribosome independently of interactions with the mRNA 5′ 7-methyl G cap.”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [36]
The Results report that the tripartite leader enhances mRNA translation late after infection. The Discussion says it may act during translation initiation, but explicitly leaves its mechanism unclear; it does not establish an internal ribosome entry site or recruitment independent of the 5′ cap. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTPL contains an IRES that allows it to recruit a ribosome independently of interactions with the 5′ 7-methyl G cap of mRNA.
“This research [43,44] indicates that TPL contains an IRES due to which TPL is capable of recruiting a ribosome, independently of interactions with the 5′ 7-methyl G cap of mRNA.”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [43]
The Results report that the tripartite leader enhances translation late after infection, and the Discussion suggests it may act during initiation. But the Discussion says its point of action is unclear; our copy does not establish that it contains an IRES or recruits ribosomes independently of the 5′ cap (page numbers unavailable). (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe adenovirus tripartite leader (TPL) functions as an enhancer for translation of viral late-gene mRNAs and is thought to initiate translation of late adenoviral mRNAs in a cap-independent manner.
“The tripartite leader (TPL) of the adenovirus is known to function as an enhancer for translation of viral late-gene mRNAs and is thought to have an ability to initiate translation of late adenoviral mRNAs in a cap-independent manner [43,44].”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [43]
The Discussion (page not provided) reports that a nearly intact tripartite leader increased translation efficiency about fivefold late after adenovirus infection, supporting its role as a translational enhancer. The paper does not say that the leader initiates translation in a cap-independent manner; its discussion of the mechanism remains speculative. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn prior studies, the 5′UTR sequence of TPL consisted of 245 nucleotides and had a complex secondary structure.
“The 5′UTR sequence of TPL consisted of 245 nucleotides in those studies and had a complex secondary structure.”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [43]
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Research works printed but not linked: 2
- [1]Berget, S. M., Moore, C. & Sharp, P. A. (1977) Proc. Natl. Acad. Sci. USA 74, 3171–3175.
- [28]Scott, M. P. & Pardue, M. L. (1981) Proc. Natl. Acad. Sci. USA 78, 3353–3357.
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Pham, P. L., Kamen, A., & Durocher, Y. (2006) · Molecular Biotechnology · doi:10.1385/mb:34:2:225 · Cited by 236 · 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
Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA
Kirshina, A., Vasileva, O., Kunyk, D., Seregina, K., Muslimov, A., Ivanov, R., & Reshetnikov, V. (2023) · Biomolecules · doi:10.3390/biom13111677 · Cited by 26 · see citing works
- Authors
- Logan, J., & Shenk, T.
- ORCID
- Shenk, T
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1984-06
- Volume
- 81
- Issue
- 12
- Pages
- 3655-3659
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC345277
- OpenAlex
- W2003113791
- Cited by
- 198
- References
- 0
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 1 · 2013: 2
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (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 › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- adenovirus type 5, E1A gene, viral gene expression
- MeSH terms
- Adenoviruses, Human, Base Sequence, Gene Expression Regulation, Mutation, RNA, Messenger, RNA, Viral, Protein Biosynthesis, Virus Replication
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