YTHDF proteins and m<SUP>6</SUP>A-RNA clients undergo autophagic turnover during contact inhibition
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00640524" target="_blank" >RIV/68378050:_____/25:00640524 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.celrep.2025.116188" target="_blank" >https://doi.org/10.1016/j.celrep.2025.116188</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.celrep.2025.116188" target="_blank" >10.1016/j.celrep.2025.116188</a>
Alternative languages
Result language
angličtina
Original language name
YTHDF proteins and m<SUP>6</SUP>A-RNA clients undergo autophagic turnover during contact inhibition
Original language description
The YTHDF protein family plays acritical role in cancer development by recognizing and regulating the stability of N6-methyladenosine (m(6)A)-modified RNA. Here, we reveal an autophagy-dependent mechanism controlling YTHDF protein levels. Using contact inhibition as a cellular model system, we show YTHDF proteins to be rapidly degraded, coinciding with increased autophagy and decreased mTOR activity. Upon pharmacological mTOR inhibition, YTHDF2 is also downregulated via lysosomal degradation. YTHDF2 selectively interacts with the autophagy modifier GABARAP L2 through LC3-interacting region (LIR) motifs in its unstructured N-and C-terminal regions. Autophagic YTHDF2 downregulation results in the co-degradation of its bound m(6)A-modi-fied RNA clients. While YTHDF depletion induces cell death in contact-inhibition-deficient HCT116 cancer cells, contact-inhibited MRC5 and RPE1 cells remain unaffected. Our findings uncover a regulatory pathway that governs YTHDF protein stability with significant implications for cancer biology and cell fate determination and suggest the existence of an autophagy-mediated degradation pathway for m(6)A-modified RNA.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LM2023036" target="_blank" >LM2023036: Czech Centre for Phenogenomics</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Reports
ISSN
2639-1856
e-ISSN
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Volume of the periodical
44
Issue of the periodical within the volume
9
Country of publishing house
GB - UNITED KINGDOM
Number of pages
30
Pages from-to
116188
UT code for WoS article
001595337400004
EID of the result in the Scopus database
2-s2.0-105013848046