Diadenosine Tetraphosphate (Ap4A) Serves as a 5′ RNA Cap in Mammalian Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00582740" target="_blank" >RIV/61388963:_____/24:00582740 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/24:10487640
Result on the web
<a href="https://doi.org/10.1002/anie.202314951" target="_blank" >https://doi.org/10.1002/anie.202314951</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/anie.202314951" target="_blank" >10.1002/anie.202314951</a>
Alternative languages
Result language
angličtina
Original language name
Diadenosine Tetraphosphate (Ap4A) Serves as a 5′ RNA Cap in Mammalian Cells
Original language description
The recent expansion of the field of RNA chemical modifications has changed our understanding of post-transcriptional gene regulation. Apart from internal nucleobase modifications, 7-methylguanosine was long thought to be the only eukaryotic RNA cap. However, the discovery of non-canonical RNA caps in eukaryotes revealed a new niche of previously undetected RNA chemical modifications. We are the first to report the existence of a new non-canonical RNA cap, diadenosine tetraphosphate (Ap4A), in human and rat cell lines. Ap4A is the most abundant dinucleoside polyphosphate in eukaryotic cells and can be incorporated into RNA by RNA polymerases as a non-canonical initiating nucleotide (NCIN). Using liquid chromatography-mass spectrometry (LC-MS), we show that the amount of capped Ap4A-RNA is independent of the cellular concentration of Ap4A. A decapping enzyme screen identifies two enzymes cleaving Ap4A-RNA,NUDT2 and DXO, both of which also cleave other substrate RNAs in vitro. We further assess the translatability and immunogenicity of Ap4A-RNA and show that although it is not translated, Ap4A-RNA is recognized as self by the cell and does not elicit an immune response, making it a natural component of the transcriptome. Our findings open a previously unexplored area of eukaryotic RNA regulation.
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
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Angewandte Chemie - International Edition
ISSN
1433-7851
e-ISSN
1521-3773
Volume of the periodical
63
Issue of the periodical within the volume
6
Country of publishing house
DE - GERMANY
Number of pages
7
Pages from-to
e202314951
UT code for WoS article
001108232100001
EID of the result in the Scopus database
2-s2.0-85177209798