---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '21914'
abstract:
- lang: eng
  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.'
acknowledged_ssus:
- _id: MassSpec
- _id: LifeSc
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. "
article_number: aea7828
article_processing_charge: Yes
article_type: original
author:
- first_name: Mingyue
  full_name: Li, Mingyue
  id: 01f96916-0235-11eb-9379-a323192643b7
  last_name: Li
- first_name: Monika
  full_name: Chodasiewicz, Monika
  last_name: Chodasiewicz
- first_name: Malavika
  full_name: Muraleedharan, Malavika
  last_name: Muraleedharan
- first_name: Israel M.
  full_name: Lopez, Israel M.
  last_name: Lopez
- first_name: Michal
  full_name: Gorka, Michal
  last_name: Gorka
- first_name: Olga
  full_name: Kerber, Olga
  last_name: Kerber
- first_name: Saqer S.
  full_name: Alotaibi, Saqer S.
  last_name: Alotaibi
- first_name: Andrew D.L.
  full_name: Nelson, Andrew D.L.
  last_name: Nelson
- first_name: Rene
  full_name: Lenobel, Rene
  last_name: Lenobel
- first_name: Jaroslava
  full_name: Friedecká, Jaroslava
  last_name: Friedecká
- first_name: Aleksandra
  full_name: Skirycz, Aleksandra
  last_name: Skirycz
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  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>
  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>
  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.
  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.
  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>.
  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).
corr_author: '1'
date_created: 2026-05-24T22:01:31Z
date_published: 2026-05-08T00:00:00Z
date_updated: 2026-06-02T14:36:41Z
day: '08'
ddc:
- '580'
department:
- _id: JiFr
doi: 10.1126/sciadv.aea7828
external_id:
  pmid:
  - '42102187'
file:
- access_level: open_access
  checksum: 75b8ef2db078652c750e34e9cd98a808
  content_type: application/pdf
  creator: dernst
  date_created: 2026-06-02T14:33:55Z
  date_updated: 2026-06-02T14:33:55Z
  file_id: '21941'
  file_name: 2026_ScienceAdv_Li2.pdf
  file_size: 2014452
  relation: main_file
  success: 1
file_date_updated: 2026-06-02T14:33:55Z
has_accepted_license: '1'
intvolume: '        12'
issue: '19'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 8f347782-16d5-11f0-9cad-8c19706ee739
  grant_number: '101142681'
  name: Cyclic nucleotides as second messengers in plants
- _id: 7bcece63-9f16-11ee-852c-ae94e099eeb6
  grant_number: P37051
  name: Guanylate cyclase activity of TIR1/AFBs auxin receptors
publication: Science Advances
publication_identifier:
  eissn:
  - 2375-2548
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: Biogenesis and downstream effects of 3',5' and 2',3' cAMP isomers in plants
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2026'
...