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Series GSE246026 Query DataSets for GSE246026
Status Public on Aug 16, 2024
Title RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Other
Summary Mitochondria are essential regulators of innate immunity. They generate long double-stranded RNAs (mt-dsRNAs) and release them to the cytosol to trigger immune response under pathological stress conditions. Yet, the regulation of these self-immunogenic RNAs remains largely unknown. Here, we employ CRISPR screening on RNA-binding proteins residing in mitochondria and identify NOP2/Sun RNA methyltransferase 4 (NSUN4) as a key regulator of mt-dsRNA expression. We find that NSUN4 induces 5-methylcytosine (m5C) modification on mitochondrial RNAs, especially on the termini of light-strand long noncoding RNAs. These m5C-modified RNAs are recognized by complement C1q binding protein (C1QBP), which recruits polyribonucleotide nucleotidyltransferase to facilitate RNA turnover. Suppression of NSUN4 or C1QBP results in increased mt-dsRNA expression while C1QBP deficiency also leads to increased cytosolic mt-dsRNAs and subsequent immune activation. Collectively, our study unveils the mechanism underlying the selective degradation of light-strand mitochondrial RNAs and establishes a molecular mark for mitochondrial RNA decay and cytosolic release.
 
Overall design RNA Bisulfite-seq following NSUN4, C1QBP or PNPT1 downregulation in HEK-293T cells.
 
Contributor(s) Kim S, Tan S, Kim Y
Citation(s) 39019044
Submission date Oct 23, 2023
Last update date Aug 17, 2024
Contact name Sujin Kim
E-mail(s) sujinkim23aug@gmail.com
Organization name KAIST
Department Chemical and Biomolecular Engineering
Street address 291, Daehak-ro
City Daejeon
ZIP/Postal code 34141
Country South Korea
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (14)
GSM7854077 293T, sgNC, biol rep 1
GSM7854078 293T, sgNC, biol rep 2
GSM7854079 293T, sgNSUN4, biol rep 1
Relations
BioProject PRJNA1031131

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Supplementary file Size Download File type/resource
GSE246026_RAW.tar 2.2 Gb (http)(custom) TAR (of COV)
SRA Run SelectorHelp
Raw data are available in SRA

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