U1snRNP-mediated suppression of polyadenylation in conjunction with the RNA structure controls poly (A) site selection in foamy viruses
Open accessAbstract
Background: During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal. Results: Here, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation. Conclusion: Recently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5’end of their RNA. At the 3’end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In both HIV-1 and foamy viruses, the primary factor in splice-site-mediated suppression is the binding of U1 snRNP to the major splice donor site.
“Furthermore, in both HIV-1 and foamy viruses, the primary factor in splice-site-mediated suppression is the binding of U1 small nuclear ribonucleoprotein (U1 snRNP), part of the spliceosome complex, to the major splice donor site (Ashe et al. 1995, 1997, 2000, Schrom et al. 2013).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Schrom et al. 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mfold web server for nucleic acid folding and hybridization prediction
Zuker, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg595 · Cited by 13,404 · see citing works
Human Splicing Finder: an online bioinformatics tool to predict splicing signals
Desmet, F.-O., Hamroun, D., Lalande, M., Collod‐Béroud, G., Claustres, M., & Béroud, C. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp215 · Cited by 2,500 · see citing works
Seiki, M., Hattori, S., Hirayama, Y., & Yoshida, M. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.12.3618 · Cited by 1,525 · see citing works
Splicing regulation: From a parts list of regulatory elements to an integrated splicing code
Wang, Z., & Burge, C. B. (2008) · RNA · doi:10.1261/rna.876308 · Cited by 1,076 · see citing works
Zhao, J., Hyman, L. E., & Moore, C. L. (1999) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.63.2.405-445.1999 · Cited by 1,024 · see citing works
Pre-mRNA Processing Reaches Back toTranscription and Ahead to Translation
Moore, M. J., & Proudfoot, N. J. (2009) · Cell · doi:10.1016/j.cell.2009.02.001 · Cited by 835 · see citing works
Merino, E. J., Wilkinson, K. A., Coughlan, J. L., & Weeks, K. M. (2005) · Journal of the American Chemical Society · doi:10.1021/ja043822v · Cited by 791 · see citing works
Wilkinson, K. A., Merino, E. J., & Weeks, K. M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.249 · Cited by 775 · see citing works
U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
Kaida, D., Berg, M. G., Younis, I., Kasim, M., Singh, L. N., Wan, L., & Dreyfuss, G. (2010) · Nature · doi:10.1038/nature09479 · Cited by 638 · see citing works
Molecular mechanisms of eukaryotic pre-mRNA 3′ end processing regulation
Millevoi, S., & Vagner, S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1176 · Cited by 393 · see citing works
Mortimer, S., & Weeks, K. M. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0704028 · Cited by 358 · see citing works
3′ end mRNA processing: molecular mechanisms and implications for health and disease
Danckwardt, S., Hentze, M. W., & Kulozik, A. E. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601932 · Cited by 296 · see citing works
Cleavage site determinants min the mammalian polydenylation signal
Chen, F., MacDonald, C. C., & Wilusf, J. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.14.2614 · Cited by 189 · see citing works
Using reliability information to annotate RNA secondary structures
Zuker, M., & Jacobson, A. B. (1998) · RNA · doi:10.1017/s1355838298980116 · Cited by 174 · see citing works
Human foamy virus reverse transcription that occurs late in the viral replication cycle
Moebes, A., Enssle, J., Bieniasz, P. D., Heinkelein, M., Lindemann, D., Bock, M., McClure, M. O., & Rethwilm, A. (1997) · Journal of Virology · doi:10.1128/jvi.71.10.7305-7311.1997 · Cited by 156 · see citing works
Löchelt, M., Zentgraf, H., & gel, R. M. F. U. (1991) · Virology · doi:10.1016/0042-6822(91)90820-2 · Cited by 154 · see citing works
Lentivirus Replication and Regulation
Tang, H., Kuhen, K., & Wong‐Staal, F. (1999) · Annual Review of Genetics · doi:10.1146/annurev.genet.33.1.133 · Cited by 144 · see citing works
Ashe, M. P., Griffin, P., James, W., & Proudfoot, N. J. (1995) · Genes & Development · doi:10.1101/gad.9.23.3008 · Cited by 125 · see citing works
Ashe, M. P., Pearson, L. H., & Proudfoot, N. J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.18.5752 · Cited by 118 · see citing works
Muranyi, W., & Flügel, R. M. (1991) · Journal of Virology · doi:10.1128/jvi.65.2.727-735.1991 · Cited by 109 · see citing works
Das, A. T., Klaver, B., & Berkhout, B. (1999) · Journal of Virology · doi:10.1128/jvi.73.1.81-91.1999 · Cited by 107 · see citing works
RNAML: A standard syntax for exchanging RNA information
Waugh, A., Gendron, P., Altman, R. B., Brown, J. W., Case, D. A., Gautheret, D., Harvey, S. C., Leontis, N. B., Westbrook, J., Westhof, É., et al. (2002) · RNA · doi:10.1017/s1355838202028017 · Cited by 102 · see citing works
Rigo, F., & Martinson, H. G. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01410-07 · Cited by 100 · see citing works
The HTLV-I rex response element mediates a novel form of mRNA polyadenylation
Ahmed, Y. F., Gilmartin, G. M., Hanly, S. M., Nevins, J. R., & Greene, W. C. (1991) · Cell · doi:10.1016/0092-8674(91)90502-p · Cited by 96 · see citing works
Activation of HIV‐1 pre‐mRNA 3′ processing in vitro requires both an upstream element and TAR.
Gilmartin, G. M., Fleming, E. S., & Oetjen, J. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05542.x · Cited by 84 · see citing works
Genomic organization and expression of simian foamy virus type 3 (SFV-3)
Renne, R., Friedl, E. M., Schweizer, M., Fleps, U., Turek, R., & Neumann‐Haefelin, D. (1992) · Virology · doi:10.1016/0042-6822(92)90026-l · Cited by 79 · see citing works
Stem-loop 1 of the U1 snRNP plays a critical role in the suppression of HIV-1 polyadenylation
Ashe, M., Furger, A., & Proudfoot, N. J. (2000) · RNA · doi:10.1017/s1355838200991957 · Cited by 68 · see citing works
Occlusion of the HIV poly(A) site
Weichs an der Glon, C., Monks, J., & Proudfoot, N. J. (1991) · Genes & Development · doi:10.1101/gad.5.2.244 · Cited by 68 · see citing works
A Rapid and Quantitative Assay for Measuring Neighboring Gene Activation by Vector Proviruses
Hendrie, P. C., Huo, Y., Stolitenko, R. B., & Russell, D. W. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300398 · Cited by 49 · see citing works
Foamy Virus Transactivation and Gene Expression
Löchelt, M. (2003) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-55701-9_2 · Cited by 49 · see citing works
Foamy virus nuclear RNA export is distinct from that of other retroviruses
Bodem, J., Schied, T., Gabriel, R., Rammling, M., & Rethwilm, A. (2011) · Journal of Virology · doi:10.1128/jvi.01518-10 · Cited by 44 · see citing works
Self-citationPolyadenylation releases mRNA from RNA polymerase II in a process that is licensed by splicing
Rigo, F., & Martinson, H. G. (2009) · RNA · doi:10.1261/rna.1409209 · Cited by 44 · see citing works
cis-acting regulatory regions in the long terminal repeat of simian foamy virus type 1
Mergia, A., Pratt-Lowe, E., Shaw, K. E., Renshaw-Gegg, L. W., & Luciw, P. A. (1992) · Journal of Virology · doi:10.1128/jvi.66.1.251-257.1992 · Cited by 44 · see citing works
Bohne, J. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki185 · Cited by 43 · see citing works
Self-citationAsang, C., Hauber, I., & Schaal, H. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkm1147 · Cited by 41 · see citing works
Furger, A., Monks, J., & Proudfoot, N. J. (2001) · Journal of Virology · doi:10.1128/jvi.75.23.11735-11746.2001 · Cited by 40 · see citing works
Bodem, J., Löchelt, M., Delius, H., & Flügel, R. M. (1998) · Virology · doi:10.1006/viro.1998.9113 · Cited by 38 · see citing works
Self-citationHeinkelein, M., Thurow, J., Dressler, M., Imrich, H., Neumann‐Haefelin, D., McClure, M. O., & Rethwilm, A. (2000) · Journal of Virology · doi:10.1128/jvi.74.7.3141-3148.2000 · Cited by 38 · see citing works
Hartl, M. J., Bodem, J., Jochheim, F., Rethwilm, A., ROSCH, P. J., & Wöhrl, B. M. (2011) · Journal of Virology · doi:10.1128/jvi.02211-10 · Cited by 34 · see citing works
Self-citationBohne, J., & Kräusslich, H. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00277-7 · Cited by 31 · see citing works
Self-citationGuan, F., Caratozzolo, R. M., Goraczniak, R. M., Ho, E. S., & Gunderson, S. (2007) · RNA · doi:10.1261/rna.756707 · Cited by 29 · see citing works
Russell, R. A., Zeng, Y., Erlwein, O. W., Cullen, B. R., & McClure, M. O. (2001) · Journal of Virology · doi:10.1128/jvi.75.15.6817-6824.2001 · Cited by 27 · see citing works
A complex immunodeficiency is based on U1 snRNP‐mediated poly(A) site suppression
Langemeier, J., Schrom, E.-M., Rabner, A., Radtke, M., Zychlinski, D., Saborowski, A. L., Bohn, G., Mandel‐Gutfreund, Y., Bodem, J., Klein, C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.252 · Cited by 24 · see citing works
Self-citationZychlinski, D., Erkelenz, S., Melhorn, V., Baum, C., Schaal, H., & Bohne, J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp694 · Cited by 24 · see citing works
Self-citationRegulation of Retroviral Polyadenylation
Schrom, E.-M., Moschall, R., Schuch, A., & Bodem, J. (2013) · Advances in virus research · doi:10.1016/b978-0-12-408116-1.00001-x · Cited by 15 · see citing works
Self-citationYang, P., Zemba, M., Aboud, M., Flügel, R. M., & Löchelt, M. (1997) · Virus Genes · doi:10.1023/a:1007994527345 · Cited by 15 · see citing works
HIV-1 as RNA evolution machine
Berkhout, B. (2011) · RNA Biology · doi:10.4161/rna.8.2.14801 · Cited by 13 · see citing works
Liu, W., Backes, P., & Löchelt, M. (2009) · Virology · doi:10.1016/j.virol.2009.08.028 · Cited by 8 · see citing works
Cleavinger, P. J., Kandala, J. C., & Guntaka, R. V. (1997) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Coffin JM Hughes SH Varmus HE 1997 Retroviruses Cold Spring Habor Laboratory Press 21433340
Cited by
Sorted by citations
Venters, C. C., Oh, J., Di, C., So, B. R., & Dreyfuss, G. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032235 · Cited by 72 · see citing works
Understanding retroviral life cycle and its genomic RNA packaging
Chameettachal, A., Mustafa, F., & Rizvi, T. A. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167924 · Cited by 41 · see citing works
Koziol, U., Radío, S., Smircich, P., Zarowiecki, M., Fernández, C., & Brehm, K. (2015) · Genome Biology and Evolution · doi:10.1093/gbe/evv126 · Cited by 26 · see citing works
Cauliflower mosaic virus Transcriptome Reveals a Complex Alternative Splicing Pattern
Bouton, C. R., Geldreich, A., Ramel, L., Ryabova, L. A., Dimitrova, M., & Keller, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132665 · Cited by 16 · see citing works
Foamy Virus Protein—Nucleic Acid Interactions during Particle Morphogenesis
Hamann, M. V., & Lindemann, D. (2016) · Viruses · doi:10.3390/v8090243 · Cited by 15 · see citing works
Core spliceosomal Sm proteins as constituents of cytoplasmic mRNPs in plants
Hyjek‐Składanowska, M., Bajczyk, M., Gołębiewski, M., Nuc, P., Kołowerzo‐Lubnau, A., Jarmołowski, A., & Smoliński, D. J. (2020) · The Plant Journal · doi:10.1111/tpj.14792 · Cited by 9 · see citing works
Wagner, T., & Bodem, J. (2016) · Archives of Virology · doi:10.1007/s00705-016-3206-z · Cited by 6 · see citing works
Self-citationBeyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication
Jehad, M. A., Ali, L. M., Pillai, V. N., Prabhu, S. G., Mustafa, F., & Rizvi, T. A. (2026) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuaf066 · Cited by 5 · see citing works
“Furthermore, in both HIV-1 and foamy viruses, the primary factor in splice-site-mediated suppression is the binding of U1 small nuclear ribonucleoprotein (U1 snRNP), part of the spliceosome complex, to the major splice donor site (Ashe et al. 1995 , 1997 , 2000 , Schrom et al. 2013 ).”
A purine-rich element in foamy virus pol regulates env splicing and gag/pol expression
Moschall, R., Denk, S., Erkelenz, S., Schenk, C., Schaal, H., & Bodem, J. (2017) · Retrovirology · doi:10.1186/s12977-017-0337-6 · Cited by 4 · see citing works
Self-citationNew windows into retroviral RNA structures
Jayaraman, D., & Kenyon, J. C. (2018) · Retrovirology · doi:10.1186/s12977-018-0393-6 · Cited by 4 · see citing works
Specific RNA–protein interactions in the replication of foamy viruses (FVs)
Rethwilm, A. (2013) · Current Opinion in Virology · doi:10.1016/j.coviro.2013.09.003 · Cited by 3 · see citing works
Uhl, L. K., & Fasina, O. O. (2025) · PubMed Central · doi:10.3390/v17070984 · Cited by 1 · see citing works
Méreau, A., Lerivray, H., Viet, J., Hardy, S., Paillard, L., & Audic, Y. (2025) · Biochimie · doi:10.1016/j.biochi.2025.07.009
- Authors
- Schrom, E.-M., Moschall, R., Hartl, M. J., Weitner, H., Fecher, D., Langemeier, J., Bohne, J., Wöhrl, B. M., & Bodem, J.
- Affiliations
- University of Würzburg (DE)
- University of Bayreuth (DE)
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Bodem, Jochen
- Venue
- Retrovirology
- Published
- 2013-05-29
- Volume
- 10
- Issue
- 1
- Pages
- 55-55
- ISSN
- 1742-4690 (ISSN-L)
- PMC
- PMC3694450
- OpenAlex
- W2134714431
- Cited by
- 14
- References
- 50
- Citations by year
- 2025: 3 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Retrovirology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (Wo630/7-3)
- 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 › RNA regulation and disease
- Keywords
- polyadenylation site selection, poly(A) site, foamy virus, long terminal repeat, RNA secondary structure, 5' LTR, 3' LTR, RNA cleavage
- MeSH terms
- Animals, Cell Line, Cricetinae, Nucleic Acid Conformation, Poly A, RNA, Small Nuclear, RNA, Viral, Spumavirus, Terminal Repeat Sequences, RNA Splice Sites, Polyadenylation, RNA 3' Polyadenylation Signals
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
