The p53 mRNA exhibits riboswitch-like features under DNA damage conditions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F25%3A00080437" target="_blank" >RIV/00209805:_____/25:00080437 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2589004225018164?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2589004225018164?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.isci.2025.113555" target="_blank" >10.1016/j.isci.2025.113555</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The p53 mRNA exhibits riboswitch-like features under DNA damage conditions

Popis výsledku v původním jazyce

RNA riboswitch structures control prokaryotic gene expression in response to changes in the cellular environment, but how this concept has evolved in mammalian cells is yet little known. Here, we describe the riboswitch-like features of the p53 mRNA that controls p53 synthesis following DNA damage. The conserved BOX-I stem-loop in the 5&apos; coding sequence acts as an aptamer that controls the folding of a compact downstream MDM2-binding p53 mRNA structure. MDM2 brings the p53 mRNA to the ribosome and promotes p53 synthesis. High-throughput in-cell RNA structural probing and in vitro RNA-RNA and RNA-protein interactions show how the cancer-associated synonymous mutation in codon 22 (CASM22) of the BOX-I aptamer stabilizes the p53 mRNA structure and prevents the formation of the MDM2-binding platform. However, the CASM22 does not affect p53 mRNA folding during the unfolded protein response, demonstrating the specificity by which the CASM22 targets the p53 DNA damage response.

Název v anglickém jazyce

The p53 mRNA exhibits riboswitch-like features under DNA damage conditions

Popis výsledku anglicky

RNA riboswitch structures control prokaryotic gene expression in response to changes in the cellular environment, but how this concept has evolved in mammalian cells is yet little known. Here, we describe the riboswitch-like features of the p53 mRNA that controls p53 synthesis following DNA damage. The conserved BOX-I stem-loop in the 5&apos; coding sequence acts as an aptamer that controls the folding of a compact downstream MDM2-binding p53 mRNA structure. MDM2 brings the p53 mRNA to the ribosome and promotes p53 synthesis. High-throughput in-cell RNA structural probing and in vitro RNA-RNA and RNA-protein interactions show how the cancer-associated synonymous mutation in codon 22 (CASM22) of the BOX-I aptamer stabilizes the p53 mRNA structure and prevents the formation of the MDM2-binding platform. However, the CASM22 does not affect p53 mRNA folding during the unfolded protein response, demonstrating the specificity by which the CASM22 targets the p53 DNA damage response.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA23-06884S" target="_blank" >GA23-06884S: Charakterizace ribozomu překládajícího pre-spliced mRNA pro syntézu antigenních peptidových substrátů pro dráhu MHC-I</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

iScience

ISSN

2589-0042

e-ISSN

2589-0042

Svazek periodika

28

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

113555

Kód UT WoS článku

001585499900001

EID výsledku v databázi Scopus

2-s2.0-105017073253