Sulfonated inhibitors of the RNA editing ligases validate the essential role of the MRP1/2 proteins in kinetoplastid RNA editing

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F20%3A43901106" target="_blank" >RIV/60076658:12310/20:43901106 - isvavai.cz</a>

Alternative codes found

RIV/60077344:_____/20:00538704

Result on the web

<a href="https://rnajournal.cshlp.org/content/26/7/827.full.pdf" target="_blank" >https://rnajournal.cshlp.org/content/26/7/827.full.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1261/rna.075598.120" target="_blank" >10.1261/rna.075598.120</a>

Result language

angličtina

Original language name

Sulfonated inhibitors of the RNA editing ligases validate the essential role of the MRP1/2 proteins in kinetoplastid RNA editing

Original language description

The RNA editing core complex (RECC) catalyzes mitochondrial U-insertion/deletion mRNA editing in trypanosomatid flagellates. Some naphthalene-based sulfonated compounds, such as C35 and MrB, competitively inhibit the auto-adenylylation activity of an essential RECC enzyme, kinetoplastid RNA editing ligase 1 (KREL1), required for the final step in editing. Previous studies revealed the ability of these compounds to interfere with the interaction between the editosome and its RNA substrates, consequently affecting all catalytic activities that comprise RNA editing. This observation implicates a critical function for the affected RNA binding proteins in RNA editing. In this study, using the inhibitory compounds, we analyzed the composition and editing activities of functional editosomes and identified the mitochondrial RNA binding proteins 1 and 2 (MRP1/2) as their preferred targets. While the MRP1/2 heterotetramer complex is known to bind guide RNA and promote annealing to its cognate pre-edited mRNA, its role in RNA editing remained enigmatic. We show that the compounds affect the association between the RECC and MRP1/2 heterotetramer. Furthermore, RECC purified post-treatment with these compounds exhibit compromised in vitro RNA editing activity that, remarkably, recovers upon the addition of recombinant MRP1/2 proteins. This work provides experimental evidence that the MRP1/2 heterotetramer is required for in vitro RNA editing activity and substantiates the hypothesized role of these proteins in presenting the RNA duplex to the catalytic complex in the initial steps of RNA editing.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA204%2F09%2F1667" target="_blank" >GA204/09/1667: Characterization of a novel protein complex involved in RNA processing and editing in the mitochondrion of Trypanosoma brucei</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

RNA-A Publication of the RNA Society

ISSN

1355-8382

e-ISSN

—

Volume of the periodical

26

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

827-835

UT code for WoS article

000541897400006

EID of the result in the Scopus database

2-s2.0-85086682655