 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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)
|
| GSM7854080 |
293T, sgNSUN4, biol rep 2 |
| GSM7854081 |
293T, siLuc, biol rep 1 |
| GSM7854082 |
293T, siLuc, biol rep 2 |
| GSM7854083 |
293T, siLuc, biol rep 3 |
| GSM7854084 |
293T, siPNPase, biol rep 1 |
| GSM7854085 |
293T, siPNPase, biol rep 2 |
| GSM7854086 |
293T, siPNPase, biol rep 3 |
| GSM8283800 |
293T, siLuc-C1QBP, biol rep 1 |
| GSM8283801 |
293T, siLuc-C1QBP, biol rep 2 |
| GSM8283802 |
293T, siC1QBP, biol rep 1 |
| GSM8283803 |
293T, siC1QBP, biol rep 2 |
|
| Relations |
| BioProject |
PRJNA1031131 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246026_RAW.tar |
2.2 Gb |
(http)(custom) |
TAR (of COV) |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...