Translational Efficiency Is Regulated by the Length of the 3′ Untranslated Region
Open accessAbstract
All polyadenylated mRNAs contain sequence of variable length between the coding region and the poly(A) tail. Little has been done to establish what role the length of the 3' untranslated region (3'UTR) plays in posttranscriptional regulation. Using firefly luciferase (luc) reporter mRNA in transiently transfected Chinese hamster ovary (CHO) cells, we observed that the addition of a poly(A) tail increased expression 97-fold when the length of the 3'UTR was 19 bases but that its stimulatory effect was only 2.3-fold when the length of the 3'UTR was increased to 156 bases. The effect of the luc 3'UTR on poly(A) tail function was orientation independent, suggesting that its length and not its primary sequence was the important factor. Increasing the length of the 3'UTR increased expression from poly(A)- mRNA but had little effect on poly(A)+ mRNA. To examine the effect of length on translational efficiency and mRNA stability, a 20-base sequence was introduced and reiterated downstream of the luc stop codon to generate a nested set of constructs in which the length of the 3'UTR increased from 4 to 104 bases. For poly(A)- reporter mRNA, translational efficiency in CHO cells increased 38-fold as the length of the 3'UTR increased from 4 to 104 bases. Increasing the length of the 3'UTR beyond 104 bases increased expression even further. Increasing the length of the 3'UTR also resulted in a 2.5-fold stabilization of the reporter mRNA. For poly(A)+ mRNA, the translational efficiency and mRNA half-life increased only marginally as the length of the 3'UTR increased from 27 to 161 bases. However, positioning the poly(A) tail only 7 bases downstream of the stop codon resulted in a 39-fold reduction in the rate of translation relative to a construct with a 27-base 3'UTR, which may be a consequence of the poly(A) tail-poly(A)-binding protein complex functioning as a steric block to translocating ribosomes as they approached the termination codon. The optimal length of the 3' noncoding region for maximal poly(A) tail-mediated stimulation of translation is approximately 27 bases. These data suggest that the length of the 3'UTR plays an important role in determining both the translational efficiency and the stability of an mRNA.
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The length of the 3' UTR has an effect on the stability and translational efficiency of poly(A)-negative RNA but not of poly(A)-positive RNA, for which a 27-bp 3' UTR appears to be optimal.
“As previous reports show, the length of the 3Ј UTR as such has an effect on the stability and translational efficiency of poly(A)-negative RNA but not of poly(A)-positive RNA, for which a 27-bp 3Ј UTR appears to be optimal.20”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [20]
The Results report that increasing 3′ UTR length increased translational efficiency and half-life for poly(A)-negative mRNA, while these measures varied little for poly(A)-positive mRNA over most lengths tested. The claim's categorical 'not' misses a substantial exception: a 7-base UTR sharply reduced translation of poly(A)-positive mRNA. The reported 27-base optimum is specifically for poly(A)-tail-mediated stimulation of translation. Page numbers are not provided in the supplied passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredProtein decay kinetics is a state-of-the-art tool favored over RNA kinetics for assessing RNA stability because it allows integrated recording of all relevant translational characteristics.
“Protein decay kinetics is regarded as a state-of-the-art tool favored over RNA kinetics because it allows integrated recording of all relevant translational characteristics in the function-oriented manner required for the objective of our investigations.20”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [20]
UTRs comprise regulatory regions related to mRNA stability, ribosome recognition, interaction with translational machinery components, and mRNA secondary structures.
“They comprise various regulatory regions related to mRNA stability, ribosome recognition, interaction with translational machinery components, and mRNA secondary structures (Tanguay and Gallie 1996).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Tanguay and Gallie 1996
The 5′ and 3′ UTRs regulate mRNA stability.
“The 5′- and 3′- UTRs comprising of regulatory sequence elements are known to regulate the mRNA stability.”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Tanguay and Gallie 1996
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- [21]21. Kozak, M. 1983. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol. Rev. 47: 1-45.
- [31]31. Munroe, D., and A. Jacobson. 1990. Tales of poly(A): a review. Gene 91: 151-158.
- [43]43. Steitz, J. A. 1980. RNA z RNA interactions during polypeptide chain initiation, p. 479-495. In G. Chambliss, G. R. Craven, J. Davies, K. Davies, L. Kahan, and M. Nomura (ed.), Ribosomes: structure, function and genetics. University Park Press, Baltimore.
- [44]44. Tzamarias, D., D. Alexandraki, and G. Thireos. 1986. Multiple cis -acting elements modulate the translational efficiency of GCN4 mRNA in yeast. Proc. Natl. Acad. Sci. USA 83: 4849-4853.
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- Authors
- Tanguay, R. L., & Gallie, D. R.
- Affiliations
- University of California, Riverside (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1996-01
- Volume
- 16
- Issue
- 1
- Pages
- 146-156
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC230988
- OpenAlex
- W2131548424
- Cited by
- 204
- References
- 0
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 15 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 7
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Agriculture
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Keywords
- 3' untranslated region, 3' UTR length, translation efficiency, poly(A) tail, poly(A)-binding protein, mRNA stability, post-transcriptional regulation, polyadenylation, ribosome translocation, firefly luciferase reporter, poly(A)+ mRNA, CHO cells
- MeSH terms
- Animals, Base Sequence, Cricetinae, Luciferases, Molecular Sequence Data, Ribosomes, RNA Caps, RNA Processing, Post-Transcriptional, RNA, Messenger, Transfection, Protein Biosynthesis, Gene Expression, CHO Cells
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