{"publication_status":"published","author":[{"full_name":"Li, Mingyue","id":"01f96916-0235-11eb-9379-a323192643b7","first_name":"Mingyue","last_name":"Li"},{"full_name":"Chodasiewicz, Monika","first_name":"Monika","last_name":"Chodasiewicz"},{"first_name":"Malavika","full_name":"Muraleedharan, Malavika","last_name":"Muraleedharan"},{"last_name":"Lopez","full_name":"Lopez, Israel M.","first_name":"Israel M."},{"first_name":"Michal","full_name":"Gorka, Michal","last_name":"Gorka"},{"last_name":"Kerber","first_name":"Olga","full_name":"Kerber, Olga"},{"first_name":"Saqer S.","full_name":"Alotaibi, Saqer S.","last_name":"Alotaibi"},{"full_name":"Nelson, Andrew D.L.","first_name":"Andrew D.L.","last_name":"Nelson"},{"full_name":"Lenobel, Rene","first_name":"Rene","last_name":"Lenobel"},{"full_name":"Friedecká, Jaroslava","first_name":"Jaroslava","last_name":"Friedecká"},{"last_name":"Skirycz","full_name":"Skirycz, Aleksandra","first_name":"Aleksandra"},{"orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml"}],"DOAJ_listed":"1","type":"journal_article","article_number":"aea7828","OA_place":"publisher","pmid":1,"quality_controlled":"1","article_processing_charge":"Yes","issue":"19","status":"public","acknowledgement":" We thank J. Chai and D. Yu for providing the MBP-fused L7TIR plasmid and K. Jaworski (Nicolaus Copernicus University) for the GST-­HpAC1 plasmid. We also thank M. Randuch and L. Fiedler for providing vectors for recombinant AFB5 and ADCY. We are also grateful to E. Dutkiewicz, L. Trübestein, N. Krasnici and A. Michaelis for excellent technical\r\nassistance. We acknowledge the support of the LSF Mass Spectrometry Service and the Lab\r\nSupport Facility at the Institute of Science and Technology Austria for their contributions,\r\nincluding consultation on size exclusion chromatography, LC/MS experimental design,\r\nmetabolomics sample preparation, LC/MS method optimization, data acquisition, raw data\r\nanalysis, and absolute quantification. This project is supported by the European\r\nResearch Council (ERC) under the European Union’s Horizon 2020 research and innovation\r\nprogram (101142681 CYNIPS) and Austrian Science Fund (FWF; P 37051-B), both to J.Friml.\r\nWe acknowledge the generous support of the Taif University Researchers Supporting\r\nProject: TURSP-­HC2022/02 and Max-Planck-Society to A.S. ","has_accepted_license":"1","doi":"10.1126/sciadv.aea7828","intvolume":"        12","external_id":{"pmid":["42102187"]},"publisher":"AAAS","acknowledged_ssus":[{"_id":"MassSpec"},{"_id":"LifeSc"}],"project":[{"_id":"8f347782-16d5-11f0-9cad-8c19706ee739","grant_number":"101142681","name":"Cyclic nucleotides as second messengers in plants"},{"name":"Guanylate cyclase activity of TIR1/AFBs auxin receptors","_id":"7bcece63-9f16-11ee-852c-ae94e099eeb6","grant_number":"P37051"}],"department":[{"_id":"JiFr"}],"PlanS_conform":"1","citation":{"apa":"Li, M., Chodasiewicz, M., Muraleedharan, M., Lopez, I. M., Gorka, M., Kerber, O., … Friml, J. (2026). Biogenesis and downstream effects of 3’,5’ and 2’,3’ cAMP isomers in plants. <i>Science Advances</i>. AAAS. <a href=\"https://doi.org/10.1126/sciadv.aea7828\">https://doi.org/10.1126/sciadv.aea7828</a>","ama":"Li M, Chodasiewicz M, Muraleedharan M, et al. Biogenesis and downstream effects of 3’,5’ and 2’,3’ cAMP isomers in plants. <i>Science Advances</i>. 2026;12(19). doi:<a href=\"https://doi.org/10.1126/sciadv.aea7828\">10.1126/sciadv.aea7828</a>","short":"M. Li, M. Chodasiewicz, M. Muraleedharan, I.M. Lopez, M. Gorka, O. Kerber, S.S. Alotaibi, A.D.L. Nelson, R. Lenobel, J. Friedecká, A. Skirycz, J. Friml, Science Advances 12 (2026).","chicago":"Li, Mingyue, Monika Chodasiewicz, Malavika Muraleedharan, Israel M. Lopez, Michal Gorka, Olga Kerber, Saqer S. Alotaibi, et al. “Biogenesis and Downstream Effects of 3’,5’ and 2’,3’ CAMP Isomers in Plants.” <i>Science Advances</i>. AAAS, 2026. <a href=\"https://doi.org/10.1126/sciadv.aea7828\">https://doi.org/10.1126/sciadv.aea7828</a>.","ieee":"M. Li <i>et al.</i>, “Biogenesis and downstream effects of 3’,5’ and 2’,3’ cAMP isomers in plants,” <i>Science Advances</i>, vol. 12, no. 19. AAAS, 2026.","mla":"Li, Mingyue, et al. “Biogenesis and Downstream Effects of 3’,5’ and 2’,3’ CAMP Isomers in Plants.” <i>Science Advances</i>, vol. 12, no. 19, aea7828, AAAS, 2026, doi:<a href=\"https://doi.org/10.1126/sciadv.aea7828\">10.1126/sciadv.aea7828</a>.","ista":"Li M, Chodasiewicz M, Muraleedharan M, Lopez IM, Gorka M, Kerber O, Alotaibi SS, Nelson ADL, Lenobel R, Friedecká J, Skirycz A, Friml J. 2026. Biogenesis and downstream effects of 3’,5’ and 2’,3’ cAMP isomers in plants. Science Advances. 12(19), aea7828."},"volume":12,"file_date_updated":"2026-06-02T14:33:55Z","oa_version":"Published Version","_id":"21914","oa":1,"date_published":"2026-05-08T00:00:00Z","month":"05","ddc":["580"],"publication":"Science Advances","date_updated":"2026-06-02T14:36:41Z","date_created":"2026-05-24T22:01:31Z","title":"Biogenesis and downstream effects of 3',5' and 2',3' cAMP isomers in plants","day":"08","article_type":"original","scopus_import":"1","year":"2026","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_created":"2026-06-02T14:33:55Z","access_level":"open_access","file_size":2014452,"date_updated":"2026-06-02T14:33:55Z","relation":"main_file","creator":"dernst","checksum":"75b8ef2db078652c750e34e9cd98a808","file_name":"2026_ScienceAdv_Li2.pdf","success":1,"file_id":"21941","content_type":"application/pdf"}],"OA_type":"gold","abstract":[{"text":"Cyclic adenosine monophosphate (cAMP) is a fundamental second messenger involved in diverse signaling pathways across both animals and plants. While the role of 3′,5′-cAMP has been extensively characterized, the biological significance of its structural isomer, 2′,3′-cAMP, remains largely unexplored, particularly in plants. Here, we show that 2′,3′-cAMP and 3′,5′-cAMP represent parallel signaling systems in Arabidopsis thaliana, with different enzymatic origins and largely distinct downstream effects. In vitro enzymatic assays show that plant adenylate cyclases (ACs), including AFB5 and HpAC1, produce specifically 3′,5′-cAMP from ATP, whereas the TIR domain of protein L7 also catalyzes the formation of 2′,3′-cAMP from RNA. Comprehensive multiomics analyses reveal that two isomers elicit distinct yet partially overlapping metabolic, proteomic, and transcriptional response: 2′,3′-cAMP activates broad, stress-adaptive gene expression reprogramming, while 3′,5′-cAMP fine-tunes responses related to nutrient status and cellular homeostasis. Our findings establish the existence of dual cAMP signaling systems in plants, each with specialized functions and provide insights into the complex regulatory networks governing plant physiology.","lang":"eng"}],"license":"https://creativecommons.org/licenses/by/4.0/","publication_identifier":{"eissn":["2375-2548"]},"language":[{"iso":"eng"}],"corr_author":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"}}