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An emerging technique with promise in the context of fighting HIV type 1 (HIV-1) focuses on targeting ribosomal frameshifting. A crucial \u20131 programmed ribosomal frameshift (PRF) has been observed in several pathogenic viruses, including HIV-1. Altered folds of the HIV-1 RNA frameshift element (FSE) have been shown to alter frameshifting efficiency. Here, we use RNA-As-Graphs (RAG), a graph-theory based framework for representing and analyzing RNA secondary structures, to perform conformational analysis in motif space to propose how sequence length may influence folding patterns. This combined analysis, along with all-atom modeling and experimental testing of our designed mutants, has already proven valuable for the SARS-CoV-2 FSE. As a first step to launching the same computational\/experimental approach for HIV-1, we compare prior experiments and perform SHAPE-guided 2D-fold predictions for the HIV-1 FSE embedded in increasing sequence contexts and predict structure-altering mutations. We find a highly stable upper stem and highly flexible lower stem for the core FSE, with a three-way junction connecting to other motifs at increasing lengths. In particular, we find little support for a pseudoknot or triplex interaction in the core FSE, although pseudoknots can form separately as a connective motif at longer sequences. We also identify sensitive residues in the upper stem and central loop that, when minimally mutated, alter the core stem loop folding. These insights into the FSE fold and structure-altering mutations can be further pursued by all-atom simulations and experimental testing to advance the mechanistic understanding and therapeutic strategies for HIV-1.<\/jats:p>","DOI":"10.3390\/ijms26136297","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Conformational Analysis and Structure-Altering Mutations of the HIV-1 Frameshifting Element"],"prefix":"10.3390","volume":"26","author":[{"given":"Katelyn","family":"Newton","sequence":"first","affiliation":[{"name":"University of Portland, Portland, OR 97203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, NY 10003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-2062","authenticated-orcid":false,"given":"Tamar","family":"Schlick","sequence":"additional","affiliation":[{"name":"Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, NY 10003, USA"},{"name":"Courant Institute of Mathematical Sciences, New York University, 251 Mercer St., New York, NY 10012, USA"},{"name":"New York University-East China Normal University Center for Computational Chemistry, New York University Shanghai, Shanghai 200122, China"},{"name":"Simons Center for Computational Physical Chemistry, New York University, 24 Waverly Place, Silver Building, New York, NY 10003, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","first-page":"e1","article-title":"Updated data and methods for the 2023 UNAIDS HIV estimates","volume":"95","author":"Mahy","year":"2024","journal-title":"JAIDS"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gumna, J., Antczak, M., Adamiak, R.W., Bujnicki, J.M., Chen, S.J., Ding, F., Ghosh, P., Li, J., Mukherjee, S., and Nithin, C. (2022). Computational Pipeline for Reference-Free Comparative Analysis of RNA 3D Structures Applied to SARS-CoV-2 UTR Models. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179630"},{"key":"ref_3","first-page":"535","article-title":"The frameshifting element in coronaviruses: Structure, function, and potential as a therapeutic target","volume":"46","author":"Li","year":"2025","journal-title":"Trends Sci."},{"key":"ref_4","first-page":"521","article-title":"Programmed Ribosomal Frameshifting Goes Beyond Viruses: Organisms from all three kingdoms use frameshifting to regulate gene expression, perhaps signaling a paradigm shift","volume":"1","author":"Dinman","year":"2006","journal-title":"Microbe"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.tibs.2015.03.006","article-title":"Changed in translation: mRNA recoding by -1 programmed ribosomal frameshifting","volume":"40","author":"Caliskan","year":"2015","journal-title":"Trends Biochem. Sci."},{"key":"ref_6","first-page":"7007","article-title":"Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use","volume":"44","author":"Atkins","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19776","DOI":"10.1074\/jbc.M109.085621","article-title":"Identification of a cellular factor that modulates HIV-1 programmed ribosomal frameshifting","volume":"285","author":"Kobayashi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1021\/acs.accounts.1c00316","article-title":"Targeting Ribosomal Frameshifting as an Antiviral Strategy: From HIV-1 to SARS-CoV-2","volume":"54","author":"Anokhina","year":"2021","journal-title":"Acc. Chem. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.cell.2018.12.030","article-title":"Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting","volume":"176","author":"Wang","year":"2019","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.bpj.2020.10.012","article-title":"Structure-altering mutations of the SARS-CoV-2 frameshifting RNA element","volume":"120","author":"Schlick","year":"2021","journal-title":"Biophys. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.abf3546","article-title":"Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome","volume":"372","author":"Bhatt","year":"2021","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41594-021-00653-y","article-title":"Cryo-EM and antisense targeting of the 28-kDa frameshift stimulation element from the SARS-CoV-2 RNA genome","volume":"28","author":"Zhang","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10741","DOI":"10.1074\/jbc.AC120.013449","article-title":"Structural and functional conservation of the programmed -1 ribosomal frameshift signal of SARS coronavirus 2 (SARS-CoV-2)","volume":"295","author":"Kelly","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/s41467-022-28603-2","article-title":"Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells","volume":"13","author":"Lan","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.molcel.2020.12.041","article-title":"Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms","volume":"81","author":"Huston","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1261\/rna.078825.121","article-title":"Crystal structure of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshifting pseudoknot","volume":"28","author":"Jones","year":"2021","journal-title":"RNA"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Weichseldorfer, M., Reitz, M., and Latinovic, O.S. (2021). Past HIV-1 medications and the current status of combined antiretroviral therapy options for HIV-1 patients. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111798"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/S0140-6736(03)15022-2","article-title":"Treatment of antiretroviral-drug-resistant HIV-1 infection","volume":"362","author":"Deeks","year":"2003","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.virusres.2005.10.008","article-title":"Programmed ribosomal frameshifting in HIV-1 and the SARS\u2013CoV","volume":"119","author":"Brierley","year":"2006","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1021\/bi5004926","article-title":"Structure and dynamics of the HIV-1 frameshift element RNA","volume":"53","author":"Low","year":"2014","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1128\/JVI.75.4.1834-1841.2001","article-title":"Maintenance of the Gag\/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity","volume":"75","author":"Crowe","year":"2001","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1021\/acschembio.7b00052","article-title":"HIV-1 frameshift RNA-targeted triazoles inhibit propagation of replication-competent and multi-drug-resistant HIV in human cells","volume":"12","author":"Hilimire","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"German Advisory Committee Blood (Arbeitskreis Blut), and Subgroup \u2018Assessment of Pathogens Transmissible by Blood\u2019 (2016). Human immunodeficiency virus (HIV). Trans. Med. Hemother., 43, 203.","DOI":"10.1159\/000445852"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1128\/JVI.78.4.2082-2087.2004","article-title":"The human immunodeficiency virus type 1 ribosomal frameshifting site is an invariant sequence determinant and an important target for antiviral therapy","volume":"78","author":"Biswas","year":"2004","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/0092-8674(88)90260-7","article-title":"HIV expression strategies: Ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems","volume":"55","author":"Wilson","year":"1988","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0092-8674(88)90031-1","article-title":"Signals for ribosomal frameshifting in the Rous sarcoma virus gag-pol region","volume":"55","author":"Jacks","year":"1988","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1021\/acs.biochem.4c00641","article-title":"A Cascade of Conformational Switches in SARS-CoV-2 Frameshifting: Coregulation by Upstream and Downstream Elements","volume":"64","author":"Lee","year":"2025","journal-title":"Biochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1261\/rna.080035.124","article-title":"Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: Implications to alternative conformations and their statistical structural analyses","volume":"30","author":"Dey","year":"2024","journal-title":"RNA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11404","DOI":"10.1021\/jacs.1c03003","article-title":"To knot or not to knot: Multiple conformations of the SARS-CoV-2 frameshifting RNA element","volume":"143","author":"Schlick","year":"2021","journal-title":"J. Amer. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/1050-3862(91)90013-H","article-title":"RNA pseudoknots downstream of the frameshift sites of retroviruses","volume":"8","author":"Le","year":"1991","journal-title":"Genet. Anal. Biomol. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5331","DOI":"10.1073\/pnas.082102199","article-title":"The frameshift signal of HIV-1 involves a potential intramolecular triplex RNA structure","volume":"99","author":"Dinman","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.1093\/nar\/gkf657","article-title":"Characterization of the frameshift stimulatory signal controlling a programmed \u22121 ribosomal frameshift in the human immunodeficiency virus type 1","volume":"30","author":"Dulude","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1261\/rna.5113603","article-title":"Efficiency of a programmed \u22121 ribosomal frameshift in the different subtypes of the human immunodeficiency virus type 1 group M","volume":"9","author":"Baril","year":"2003","journal-title":"RNA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nature08237","article-title":"Architecture and secondary structure of an entire HIV-1 RNA genome","volume":"460","author":"Watts","year":"2009","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6906","DOI":"10.1128\/JVI.00149-16","article-title":"Stability of HIV frameshift site RNA correlates with frameshift efficiency and decreased virus infectivity","volume":"90","author":"Becker","year":"2016","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1093\/nar\/gkg365","article-title":"Exploring the repertoire of RNA secondary motifs using graph theory; implications for RNA design","volume":"31","author":"Gan","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/bioinformatics\/btz611","article-title":"RAG-Web: RNA structure prediction\/design using RNA-As-Graphs","volume":"36","author":"Meng","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4284","DOI":"10.1038\/s41467-022-31353-w","article-title":"Length-dependent motions of SARS-CoV-2 frameshifting RNA pseudoknot and alternative conformations suggest avenues for frameshifting suppression","volume":"13","author":"Yan","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2417479122","DOI":"10.1073\/pnas.2417479122","article-title":"Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element","volume":"122","author":"Yan","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2221324120","DOI":"10.1073\/pnas.2221324120","article-title":"Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability","volume":"120","author":"Yan","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.jmb.2005.03.038","article-title":"Solution structure and thermodynamic investigation of the HIV-1 frameshift inducing element","volume":"349","author":"Staple","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1261\/rna.061655.117","article-title":"Conformational dynamics of the frameshift stimulatory structure in HIV-1","volume":"23","author":"Ritchie","year":"2017","journal-title":"RNA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.jmb.2005.04.045","article-title":"Structure of the RNA signal essential for translational frameshifting in HIV-1","volume":"349","author":"Gaudin","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.str.2018.01.001","article-title":"Structure of the 30 kDa HIV-1 RNA dimerization signal by a hybrid cryo-EM, NMR, and molecular dynamics approach","volume":"26","author":"Zhang","year":"2018","journal-title":"Structure"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/nar\/gks1254","article-title":"HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome","volume":"41","author":"Mouzakis","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.bpj.2014.12.006","article-title":"Dynamic motions of the HIV-1 frameshift site RNA","volume":"108","author":"Mouzakis","year":"2015","journal-title":"Biophys. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e95","DOI":"10.1093\/nar\/gks241","article-title":"R-CHIE: A web server and R package for visualizing RNA secondary structures","volume":"40","author":"Lai","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Jain, S., Bayrak, C.S., Petingi, L., and Schlick, T. (2018). Dual graph partitioning highlights a small group of pseudoknot-containing RNA submotifs. Genes, 9.","DOI":"10.3390\/genes9080371"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7868","DOI":"10.1128\/JVI.76.15.7868-7873.2002","article-title":"Analysis of natural variants of the human immunodeficiency virus type 1 gag-pol frameshift stem-loop structure","volume":"76","author":"Telenti","year":"2002","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7654","DOI":"10.1093\/nar\/gkp779","article-title":"Interaction of the HIV-1 frameshift signal with the ribosome","volume":"37","author":"Mazauric","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.virusres.2008.06.008","article-title":"Frameshifting RNA pseudoknots: Structure and mechanism","volume":"139","author":"Giedroc","year":"2009","journal-title":"Virus Res."},{"key":"ref_52","unstructured":"Seah, Y.L. (2017). Molecular Dynamics Simulation of RNA Ribosomal Frameshift Stimulatory Elements. [Ph.D. Thesis, Nanyang Technological University]."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1002\/jcc.10296","article-title":"A partition function algorithm for nucleic acid secondary structure including pseudoknots","volume":"24","author":"Dirks","year":"2003","journal-title":"J. Comput. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"i85","DOI":"10.1093\/bioinformatics\/btr215","article-title":"IPknot: Fast and accurate prediction of RNA secondary structures with pseudoknots using integer programming","volume":"27","author":"Sato","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1006\/jmbi.1998.2436","article-title":"A dynamic programming algorithm for RNA structure prediction including pseudoknots","volume":"285","author":"Rivas","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5498","DOI":"10.1073\/pnas.1219988110","article-title":"Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots","volume":"110","author":"Hajdin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jain, S., Tao, Y., and Schlick, T. (2020). Inverse folding with RNA-As-Graphs produces a large pool of candidate sequences with target topologies. J. Struct. Biol., 209.","DOI":"10.1016\/j.jsb.2019.107438"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ymeth.2019.03.022","article-title":"An extended dual graph library and partitioning algorithm applicable to pseudoknotted RNA structures","volume":"162","author":"Jain","year":"2019","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:37Z","timestamp":1760032897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/13\/6297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":58,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26136297"],"URL":"https:\/\/doi.org\/10.3390\/ijms26136297","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}