Role of Inosine-Uracil Base Pairs in the Canonical RNA Duplexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00101215" target="_blank" >RIV/00216224:14740/18:00101215 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.3390/genes9070324" target="_blank" >http://dx.doi.org/10.3390/genes9070324</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/genes9070324" target="_blank" >10.3390/genes9070324</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of Inosine-Uracil Base Pairs in the Canonical RNA Duplexes

Popis výsledku v původním jazyce

Adenosine to inosine (A-I) editing is the most common modification of double-stranded RNA (dsRNA). This change is mediated by adenosine deaminases acting on RNA (ADARs) enzymes with a preference of U&gt;A&gt;C&gt;G for 5' neighbor and G&gt;C=A&gt;U or G&gt;C&gt;U=A for 3' neighbor. A-I editing occurs most frequently in the non-coding regions containing repetitive elements such as ALUs. It leads to disruption of RNA duplex structure, which prevents induction of innate immune response. We employed standard and biased molecular dynamics (MD) simulations to analyze the behavior of RNA duplexes with single and tandem inosine-uracil (I-U) base pairs in different sequence context. Our analysis showed that the I-U pairs induce changes in base pair and base pair step parameters and have different dynamics when compared with standard canonical base pairs. In particular, the first I-U pair from tandem I-U/I-U systems exhibited increased dynamics depending on its neighboring 5' base. We discovered that UII sequence, which is frequently edited, has lower flexibility compared with other sequences (AII, GII, CII), hence it only modestly disrupts dsRNA. This might indicate that the UAA motifs in ALUs do not have to be sufficiently effective in preventing immune signaling.

Název v anglickém jazyce

Role of Inosine-Uracil Base Pairs in the Canonical RNA Duplexes

Popis výsledku anglicky

Adenosine to inosine (A-I) editing is the most common modification of double-stranded RNA (dsRNA). This change is mediated by adenosine deaminases acting on RNA (ADARs) enzymes with a preference of U&gt;A&gt;C&gt;G for 5' neighbor and G&gt;C=A&gt;U or G&gt;C&gt;U=A for 3' neighbor. A-I editing occurs most frequently in the non-coding regions containing repetitive elements such as ALUs. It leads to disruption of RNA duplex structure, which prevents induction of innate immune response. We employed standard and biased molecular dynamics (MD) simulations to analyze the behavior of RNA duplexes with single and tandem inosine-uracil (I-U) base pairs in different sequence context. Our analysis showed that the I-U pairs induce changes in base pair and base pair step parameters and have different dynamics when compared with standard canonical base pairs. In particular, the first I-U pair from tandem I-U/I-U systems exhibited increased dynamics depending on its neighboring 5' base. We discovered that UII sequence, which is frequently edited, has lower flexibility compared with other sequences (AII, GII, CII), hence it only modestly disrupts dsRNA. This might indicate that the UAA motifs in ALUs do not have to be sufficiently effective in preventing immune signaling.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

GENES

ISSN

2073-4425

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

324

Kód UT WoS článku

000445149700011

EID výsledku v databázi Scopus

2-s2.0-85049185757