Loss of ADAR1 protein induces changes in small RNA landscape in hepatocytes.

Autor:	Roučová K; Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic., Vopálenský V; Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic., Mašek T; Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic., Del Llano E; Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic.; Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics, CAS, 277 21 Liběchov, Czech Republic., Provazník J; GeneCore Facility, EMBL, 69117 Heidelberg, Germany., Landry JJM; GeneCore Facility, EMBL, 69117 Heidelberg, Germany., Azevedo N; GeneCore Facility, EMBL, 69117 Heidelberg, Germany., Ehler E; Department of Biology and Environmental Studies, Faculty of Education, Charles University, 116 39 Prague, Czech Republic., Beneš V; GeneCore Facility, EMBL, 69117 Heidelberg, Germany., Pospíšek M; Laboratory of RNA Biochemistry, Department of Genetics and Microbiology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic martin.pospisek@natur.cuni.cz benes@embl.de.
Jazyk:	angličtina
Zdroj:	RNA (New York, N.Y.) [RNA] 2024 Aug 16; Vol. 30 (9), pp. 1164-1183. Date of Electronic Publication: 2024 Aug 16.
DOI:	10.1261/rna.080097.124
Abstrakt:	In recent years, numerous evidence has been accumulated about the extent of A-to-I editing in human RNAs and the key role ADAR1 plays in the cellular editing machinery. It has been shown that A-to-I editing occurrence and frequency are tissue-specific and essential for some tissue development, such as the liver. To study the effect of ADAR1 function in hepatocytes, we have created Huh7.5 ADAR1 KO cell lines. Upon IFN treatment, the Huh7.5 ADAR1 KO cells show rapid arrest of growth and translation, from which they do not recover. We analyzed translatome changes by using a method based on sequencing of separate polysome profile RNA fractions. We found significant changes in the transcriptome and translatome of the Huh7.5 ADAR1 KO cells. The most prominent changes include negatively affected transcription by RNA polymerase III and the deregulation of snoRNA and Y RNA levels. Furthermore, we observed that ADAR1 KO polysomes are enriched in mRNAs coding for proteins pivotal in a wide range of biological processes such as RNA localization and RNA processing, whereas the unbound fraction is enriched mainly in mRNAs coding for ribosomal proteins and translational factors. This indicates that ADAR1 plays a more relevant role in small RNA metabolism and ribosome biogenesis. (© 2024 Roučová et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
Databáze:	MEDLINE
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