Translation factors promote the formation of two states of the closed-loop mRNP
Open accessAbstract
Efficient translation initiation and optimal stability of most eukaryotic messenger RNAs depends on the formation of a closed-loop structure and the resulting synergistic interplay between the 5' m(7)G cap and the 3' poly(A) tail. Evidence of eIF4G and Pab1 interaction supports the notion of a closed-loop mRNP, but the mechanistic events that lead to its formation and maintenance are still unknown. Here we use toeprinting and polysome profiling assays to delineate ribosome positioning at initiator AUG codons and ribosome-mRNA association, respectively, and find that two distinct stable (resistant to cap analogue) closed-loop structures are formed during initiation in yeast cell-free extracts. The integrity of both forms requires the mRNA cap and poly(A) tail, as well as eIF4E, eIF4G, Pab1 and eIF3, and is dependent on the length of both the mRNA and the poly(A) tail. Formation of the first structure requires the 48S ribosomal complex, whereas the second requires an 80S ribosome and the termination factors eRF3/Sup35 and eRF1/Sup45. The involvement of the termination factors is independent of a termination event.
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The poly(A) tail protects mRNA from degradation and is required to form a closed loop between the 5′ and 3′ ends that stimulates translation.
“It protects the mRNA from degradation15 and is required to form a closed loop between the 5′ and 3′ ends of the mRNA, a conformation that stimulates translation.16”
From Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo (2025) · cites this paper as [16]
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Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
Sonenberg, N., & Hinnebusch, A. G. (2009) · Cell · doi:10.1016/j.cell.2009.01.042 · Cited by 3,304 · see citing works
“Surprisingly, this last interaction also stimulates initiation complex (IC) formation in vitro independently of a prior termination event (Amrani et al., 2008).”
Mayr, C., & Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.06.016 · Cited by 1,613 · see citing works
Weinberg, D. E., Shah, P., Eichhorn, S. W., Hussmann, J. A., Plotkin, J. B., & Bartel, D. P. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.043 · Cited by 392 · 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
- Amrani, N., Ghosh, S., Mangus, D. A., & Jacobson, A.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Jacobson, Allan
- Venue
- Nature
- Published
- 2008-05-21
- Volume
- 453
- Issue
- 7199
- Pages
- 1276-1280
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2587346
- OpenAlex
- W2104427376
- Cited by
- 200
- References
- 0
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 16 · 2020: 5 · 2019: 9 · 2018: 7 · 2017: 12 · 2016: 15 · 2015: 16 · 2014: 20 · 2013: 10 · 2012: 9
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R37GM027757, R01GM027757)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- mRNA cap, poly(A) tail, translation initiation, eIF4G, Pab1, eIF4E, eIF3, termination factors, 80S ribosome, mRNA stability, polysome profiling
- MeSH terms
- Animals, Base Sequence, Cycloheximide, Peptide Termination Factors, Polyribosomes, Prions, Ribonucleoproteins, Ribosomal Proteins, Ribosomes, RNA Caps, RNA, Messenger, Saccharomyces cerevisiae, Protein Biosynthesis, Codon, Initiator, Saccharomyces cerevisiae Proteins, Poly(A)-Binding Proteins, Eukaryotic Initiation Factor-4G
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