---
OA_place: publisher
OA_type: hybrid
_id: '22267'
abstract:
- lang: eng
  text: Thermal pollution, whether local or driven by global warming, threatens biodiversity
    in part through its detrimental effects on reproduction. Non-coding small RNAs
    (sRNAs) are crucial for maintaining germline developmental robustness under heat
    stress. Remarkably, we uncovered that neuronal sRNAs regulate germ cells’ thermotolerance,
    affecting both spermatogenic and oogenic germlines in a cell-non-autonomous manner.
    Furthermore, we demonstrate that, in RNAi mutants, an oxygen-sensing neural circuit,
    modulated by neuropeptide signaling, antagonizes germline maintenance, likely
    reflecting the nematode’s innate association of reduced oxygen levels with food
    availability and reproductive permissive environments. Finally, we provide evidence
    that laboratory-domesticated alleles of oxygen-response genes encoding neuropeptide
    receptor NPR-1 and hexacoordinated globin GLB-5 compromise germline thermotolerance.
    Hence, our findings raise the possibility that sensory perception, independent
    of direct environmental change, modulates germline integrity, highlighting a novel
    mechanism by which neural circuits integrate environmental information to safeguard
    reproductive fitness in fluctuating environments.
acknowledgement: We thank Itai Reiger for their assistance with experiments. We thank
  Cori Bargmann (Rockefeller University) for providing introgressed strains carrying
  HW alleles of npr-1 and glb-5. Some graphics were created with Biorender.com. We
  are grateful to WormBase for providing valuable data and resources. Some strains
  were provided by the Caenorhabditis Genetics Center (CGC), which is funded by NIH
  Office of Research Infrastructure Programs (P40 OD010440). O.R. is grateful for
  the support of the Morris Kahn Foundation. C.K.E. was supported by an EMBO fellowship
  ALTF 6-2022. This work is funded by Eric and Wendy Schmidt Fund for Strategic Innovation
  Polymath Award 0140001000 (O.R.); European Research Council grant 335624 (O.R.);
  Israel Science Foundation 979/21 (Y.B.T.); and the US-Israel Binational Science
  Foundation 2023036 (Y.B.T.).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Chee Kiang
  full_name: Ewe, Chee Kiang
  last_name: Ewe
- first_name: Hanna
  full_name: Achache, Hanna
  last_name: Achache
- first_name: Hanna
  full_name: Schön, Hanna
  id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
  last_name: Schön
- first_name: Leonid
  full_name: Kontorovich, Leonid
  last_name: Kontorovich
- first_name: Guy
  full_name: Teichman, Guy
  last_name: Teichman
- first_name: Shir
  full_name: Weiss, Shir
  last_name: Weiss
- first_name: Anna
  full_name: Mogilevskaya, Anna
  last_name: Mogilevskaya
- first_name: Myriam
  full_name: Valenski, Myriam
  last_name: Valenski
- first_name: Sarit
  full_name: Anava, Sarit
  last_name: Anava
- first_name: Rutwik
  full_name: Bardapurkar, Rutwik
  last_name: Bardapurkar
- first_name: Hila
  full_name: Gingold, Hila
  last_name: Gingold
- first_name: Rachel
  full_name: Posner, Rachel
  last_name: Posner
- first_name: Olga
  full_name: Antonova, Olga
  last_name: Antonova
- first_name: Mario
  full_name: De Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: De Bono
  orcid: 0000-0001-8347-0443
- first_name: Yonatan B.
  full_name: Tzur, Yonatan B.
  last_name: Tzur
- first_name: Oded
  full_name: Rechavi, Oded
  last_name: Rechavi
citation:
  ama: Ewe CK, Achache H, Schön H, et al. Neuronal RNAi and oxygen-sensing circuit
    shape germline resilience to heat stress. <i>Current Biology</i>. 2026;36(14):3566-3579.e5.
    doi:<a href="https://doi.org/10.1016/j.cub.2026.06.016">10.1016/j.cub.2026.06.016</a>
  apa: Ewe, C. K., Achache, H., Schön, H., Kontorovich, L., Teichman, G., Weiss, S.,
    … Rechavi, O. (2026). Neuronal RNAi and oxygen-sensing circuit shape germline
    resilience to heat stress. <i>Current Biology</i>. Elsevier. <a href="https://doi.org/10.1016/j.cub.2026.06.016">https://doi.org/10.1016/j.cub.2026.06.016</a>
  chicago: Ewe, Chee Kiang, Hanna Achache, Hanna Schön, Leonid Kontorovich, Guy Teichman,
    Shir Weiss, Anna Mogilevskaya, et al. “Neuronal RNAi and Oxygen-Sensing Circuit
    Shape Germline Resilience to Heat Stress.” <i>Current Biology</i>. Elsevier, 2026.
    <a href="https://doi.org/10.1016/j.cub.2026.06.016">https://doi.org/10.1016/j.cub.2026.06.016</a>.
  ieee: C. K. Ewe <i>et al.</i>, “Neuronal RNAi and oxygen-sensing circuit shape germline
    resilience to heat stress,” <i>Current Biology</i>, vol. 36, no. 14. Elsevier,
    p. 3566–3579.e5, 2026.
  ista: Ewe CK, Achache H, Schön H, Kontorovich L, Teichman G, Weiss S, Mogilevskaya
    A, Valenski M, Anava S, Bardapurkar R, Gingold H, Posner R, Antonova O, de Bono
    M, Tzur YB, Rechavi O. 2026. Neuronal RNAi and oxygen-sensing circuit shape germline
    resilience to heat stress. Current Biology. 36(14), 3566–3579.e5.
  mla: Ewe, Chee Kiang, et al. “Neuronal RNAi and Oxygen-Sensing Circuit Shape Germline
    Resilience to Heat Stress.” <i>Current Biology</i>, vol. 36, no. 14, Elsevier,
    2026, p. 3566–3579.e5, doi:<a href="https://doi.org/10.1016/j.cub.2026.06.016">10.1016/j.cub.2026.06.016</a>.
  short: C.K. Ewe, H. Achache, H. Schön, L. Kontorovich, G. Teichman, S. Weiss, A.
    Mogilevskaya, M. Valenski, S. Anava, R. Bardapurkar, H. Gingold, R. Posner, O.
    Antonova, M. de Bono, Y.B. Tzur, O. Rechavi, Current Biology 36 (2026) 3566–3579.e5.
das_tickbox: '1'
dataavailabilitystatement: "* All NGS data are available through GEO under accession
  number GSE331410.\r\n* This paper does not report original code.\r\n* Any additional
  information required to reanalyze the data reported in this paper is available from
  the lead contact upon request."
date_created: 2026-07-12T22:02:18Z
date_published: 2026-07-20T00:00:00Z
date_updated: 2026-07-28T07:32:06Z
day: '20'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.1016/j.cub.2026.06.016
external_id:
  pmid:
  - '42409014'
file:
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language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 3566-3579.e5
pmid: 1
publication: Current Biology
publication_identifier:
  eissn:
  - 1879-0445
  issn:
  - 0960-9822
publication_status: published
publisher: Elsevier
quality_controlled: '1'
researchdata_availability: upon request
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Neuronal RNAi and oxygen-sensing circuit shape germline resilience to heat
  stress
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: 36
year: '2026'
...
---
APC_amount: 7068 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20929'
abstract:
- lang: eng
  text: Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors
    to control development, homeostasis, and aging. Here, we use proximity labeling
    to identify proteins interacting with the C. elegans FOXO DAF-16. We show that
    in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms
    a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell
    polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation
    at S249, at a conserved motif that PAR-1/human MARK2 phosphorylates in vitro.
    DAF-2 insulin-like receptor signaling stimulates DAF-16 S249 phosphorylation,
    suggesting DAF-2 activates PAR-1. DAF-2 also promotes PAR-1 expression by inhibiting
    DAF-16. PAR-1 knockdown, or DAF-16 S249A, prolong lifespan, whereas phosphomimetic
    DAF-16 S249D suppresses the longevity of daf-2 mutants. At low insulin signaling,
    DAF-16 proximity labeling highlights transcription factors, chromatin regulators,
    and DNA repair proteins. One interactor, the zinc finger/homeobox protein ZFH-2/ZFHX3,
    forms a complex with DAF-16 and prolongs lifespan. Our work provides entry points
    for hypothesis-driven studies of FOXO function and longevity.
acknowledged_ssus:
- _id: Bio
acknowledgement: We thank de Bono lab members for helpful comments on the manuscript,
  and the Mass Spec Facility at the Max Perutz Labs, notably WeiQiang Chen and Markus
  Hartl, for invaluable discussions and comments on mass spec analyses of worm samples.
  All LC-MS/MS analyses were performed on instruments of the Vienna BioCenter Core
  Facilities (VBCF). Microscopy was supported by the Scientific Services Units (SSU)
  of ISTA through resources provided by the Imaging & Optics Facility (IOF). We are
  grateful to Dr. Geraldine Seydoux (Johns Hopkins University) for worm strains and
  plasmids, and Dr. Seung-Jae V. Lee (KAIST) for RNAi clones. We are grateful to Ekaterina
  Lashmanova for designing the daf-16::TbID::mNG::3xFLAG knock-in construct and for
  her outstanding support in the lab. This work was supported by a Wellcome Investigator
  Award (209504/A/17/Z) to MdB and an ISTplus Fellowship to MA (Marie Sklodowska-Curie
  agreement No 754411).
article_number: '11355'
article_processing_charge: Yes
article_type: original
author:
- first_name: Murat
  full_name: Artan, Murat
  id: C407B586-6052-11E9-B3AE-7006E6697425
  last_name: Artan
  orcid: 0000-0001-8945-6992
- first_name: Hanna
  full_name: Schön, Hanna
  id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
  last_name: Schön
- first_name: Mario
  full_name: De Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: De Bono
  orcid: 0000-0001-8347-0443
citation:
  ama: Artan M, Schön H, de Bono M. Proximity labeling of DAF-16 FOXO highlights aging
    regulatory proteins. <i>Nature Communications</i>. 2025;16. doi:<a href="https://doi.org/10.1038/s41467-025-66409-0">10.1038/s41467-025-66409-0</a>
  apa: Artan, M., Schön, H., &#38; de Bono, M. (2025). Proximity labeling of DAF-16
    FOXO highlights aging regulatory proteins. <i>Nature Communications</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41467-025-66409-0">https://doi.org/10.1038/s41467-025-66409-0</a>
  chicago: Artan, Murat, Hanna Schön, and Mario de Bono. “Proximity Labeling of DAF-16
    FOXO Highlights Aging Regulatory Proteins.” <i>Nature Communications</i>. Springer
    Nature, 2025. <a href="https://doi.org/10.1038/s41467-025-66409-0">https://doi.org/10.1038/s41467-025-66409-0</a>.
  ieee: M. Artan, H. Schön, and M. de Bono, “Proximity labeling of DAF-16 FOXO highlights
    aging regulatory proteins,” <i>Nature Communications</i>, vol. 16. Springer Nature,
    2025.
  ista: Artan M, Schön H, de Bono M. 2025. Proximity labeling of DAF-16 FOXO highlights
    aging regulatory proteins. Nature Communications. 16, 11355.
  mla: Artan, Murat, et al. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory
    Proteins.” <i>Nature Communications</i>, vol. 16, 11355, Springer Nature, 2025,
    doi:<a href="https://doi.org/10.1038/s41467-025-66409-0">10.1038/s41467-025-66409-0</a>.
  short: M. Artan, H. Schön, M. de Bono, Nature Communications 16 (2025).
corr_author: '1'
date_created: 2026-01-04T23:01:34Z
date_published: 2025-12-11T00:00:00Z
date_updated: 2026-05-20T08:10:18Z
day: '11'
ddc:
- '570'
department:
- _id: MaDe
doi: 10.1038/s41467-025-66409-0
ec_funded: 1
external_id:
  pmid:
  - '41381452'
file:
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  file_id: '20941'
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  file_size: 1642352
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  success: 1
file_date_updated: 2026-01-05T10:58:28Z
has_accepted_license: '1'
intvolume: '        16'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 23870BE8-32DE-11EA-91FC-C7463DDC885E
  grant_number: 209504/A/17/Z
  name: Molecular mechanisms of neural circuit function
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins
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: 16
year: '2025'
...
---
OA_place: publisher
_id: '20167'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "This work was supported by EMBO (ALTF 302-2019 to Niko Amin-Wetzel),
  the FWF\r\n(ESPRIT PR1054E140 to Niko Amin-Wetzel), the European Research Council\r\n(Advanced
  Grant 269058 to Mario de Bono) and Wellcome (209504/A/17/Z\r\nInvestigator Award
  to Mario de Bono). "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Hanna
  full_name: Schön, Hanna
  id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
  last_name: Schön
citation:
  ama: Schön H. The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding
    GPCRs. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20167">10.15479/AT-ISTA-20167</a>
  apa: Schön, H. (2025). <i>The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs
    encoding GPCRs</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20167">https://doi.org/10.15479/AT-ISTA-20167</a>
  chicago: Schön, Hanna. “The ER Complex SUTU-7/MACO-1 Regulates the Fate of MRNAs
    Encoding GPCRs.” Institute of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20167">https://doi.org/10.15479/AT-ISTA-20167</a>.
  ieee: H. Schön, “The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding
    GPCRs,” Institute of Science and Technology Austria, 2025.
  ista: Schön H. 2025. The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding
    GPCRs. Institute of Science and Technology Austria.
  mla: Schön, Hanna. <i>The ER Complex SUTU-7/MACO-1 Regulates the Fate of MRNAs Encoding
    GPCRs</i>. Institute of Science and Technology Austria, 2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-20167">10.15479/AT-ISTA-20167</a>.
  short: H. Schön, The ER Complex SUTU-7/MACO-1 Regulates the Fate of MRNAs Encoding
    GPCRs, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-13T11:13:13Z
date_published: 2025-08-13T00:00:00Z
date_updated: 2026-04-07T11:50:26Z
day: '13'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MaDe
doi: 10.15479/AT-ISTA-20167
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file_date_updated: 2025-09-18T14:12:29Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa_version: Published Version
page: '171'
project:
- _id: 23870BE8-32DE-11EA-91FC-C7463DDC885E
  grant_number: 209504/A/17/Z
  name: Molecular mechanisms of neural circuit function
- _id: 23813290-32DE-11EA-91FC-C7463DDC885E
  grant_number: ALTF 302-2019
  name: Control of gene expression at the endoplasmic reticulum
publication_identifier:
  isbn:
  - 978-3-99078-061-9
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Mario
  full_name: de Bono, Mario
  id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
  last_name: de Bono
  orcid: 0000-0001-8347-0443
title: The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding GPCRs
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
_id: '7957'
abstract:
- lang: eng
  text: "Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain
    development and function and are characterized by wide genetic and clinical variability.
    In this review, we discuss the multiple factors that influence the clinical presentation
    of NDDs, with particular attention to gene vulnerability, mutational load, and
    the two-hit model. Despite the complex architecture of\r\nmutational events associated
    with NDDs, the various proteins involved appear to converge on common pathways,
    such as synaptic plasticity/function, chromatin remodelers and the mammalian target
    of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind
    these pathways will hopefully lead to the identification of candidates that could
    be targeted for treatment approaches."
acknowledgement: We wish to thank Jasmin Morandell for generously sharing Figure 2.
  This work was supported by the European Research Council Starting Grant (grant 715508
  ) to G.N.
article_processing_charge: No
article_type: original
author:
- first_name: Ilaria
  full_name: Parenti, Ilaria
  id: D93538B0-5B71-11E9-AC62-02EBE5697425
  last_name: Parenti
- first_name: Luis E
  full_name: Garcia Rabaneda, Luis E
  id: 33D1B084-F248-11E8-B48F-1D18A9856A87
  last_name: Garcia Rabaneda
- first_name: Hanna
  full_name: Schön, Hanna
  id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
  last_name: Schön
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders:
    From genetics to functional pathways. <i>Trends in Neurosciences</i>. 2020;43(8):608-621.
    doi:<a href="https://doi.org/10.1016/j.tins.2020.05.004">10.1016/j.tins.2020.05.004</a>'
  apa: 'Parenti, I., Garcia Rabaneda, L. E., Schön, H., &#38; Novarino, G. (2020).
    Neurodevelopmental disorders: From genetics to functional pathways. <i>Trends
    in Neurosciences</i>. Elsevier. <a href="https://doi.org/10.1016/j.tins.2020.05.004">https://doi.org/10.1016/j.tins.2020.05.004</a>'
  chicago: 'Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino.
    “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” <i>Trends
    in Neurosciences</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.tins.2020.05.004">https://doi.org/10.1016/j.tins.2020.05.004</a>.'
  ieee: 'I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental
    disorders: From genetics to functional pathways,” <i>Trends in Neurosciences</i>,
    vol. 43, no. 8. Elsevier, pp. 608–621, 2020.'
  ista: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. 2020. Neurodevelopmental
    disorders: From genetics to functional pathways. Trends in Neurosciences. 43(8),
    608–621.'
  mla: 'Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional
    Pathways.” <i>Trends in Neurosciences</i>, vol. 43, no. 8, Elsevier, 2020, pp.
    608–21, doi:<a href="https://doi.org/10.1016/j.tins.2020.05.004">10.1016/j.tins.2020.05.004</a>.'
  short: I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences
    43 (2020) 608–621.
corr_author: '1'
date_created: 2020-06-14T22:00:49Z
date_published: 2020-08-01T00:00:00Z
date_updated: 2026-04-02T14:36:06Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.tins.2020.05.004
ec_funded: 1
external_id:
  isi:
  - '000553090600008'
  pmid:
  - '32507511'
file:
- access_level: open_access
  checksum: 67db0251b1d415ae59005f876fcf9e34
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-25T09:43:40Z
  date_updated: 2020-11-25T09:43:40Z
  file_id: '8805'
  file_name: 2020_TrendsNeuroscience_Parenti.pdf
  file_size: 1439550
  relation: main_file
  success: 1
file_date_updated: 2020-11-25T09:43:40Z
has_accepted_license: '1'
intvolume: '        43'
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  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
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publication: Trends in Neurosciences
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title: 'Neurodevelopmental disorders: From genetics to functional pathways'
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...