rDNA breaks activate dsRNA pattern recognition through sense-antisense transcription
Chen, J.; Kim, S.; Chen, S.; Mo, Z.; Jiang, Y.; Liu, K. F.; Li, Q.; Greenberg, R. A.
Show abstract
Myriad DNA damaging chemo- and radio- therapies interfere with ribosomal RNA (rRNA) transcription and processing, yet the biological consequences of these phenomena remain unclear. Here we show that aberrant transcripts emanating from rDNA breaks engage double-stranded RNA pattern recognition receptors, melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) to activate immune signaling. rDNA damage abolishes full-length rRNA synthesis while generating truncated sense-antisense rRNA transcripts, whose accumulation is restrained by ATM and ATR kinase activities. Purification of the endogenous MDA5-filament coupled with sequencing identified complementary sense and antisense rRNA transcripts that terminate and initiate near the break site, respectively. This implicates aberrant rRNA species as a major source of damage induced endogenous ligands for dsRNA pattern recognition and establishes a mechanism by which nucleolar stress is coupled to immune signaling.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling 97%
- PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration 96%
- SDE2 Integrates into the TIMELESS-TIPIN Complex to Protect Stalled Replication Forks 96%
Similar papers in this journal
- Tetrameric INTS6-SOSS1 complex facilitates DNA:RNA hybrid autoregulation at double-strand breaks 97%
- Actin nucleators safeguard replication forks by limiting nascent strand degradation 97%
- METTL3 drives telomere targeting of TERRA lncRNA through m6A-dependent R-loop formation: a therapeutic target for ALT-positive neuroblastoma 97%
Similar papers in this journal
- Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops 96%
- Discovery and characterization of LNCSOX17 as an essential regulator in human endoderm formation 96%
- Treacle's ability to form liquid-like phase condensates is essential for nucleolar fibrillar center assembly, efficient rRNA transcription and processing, and rRNA gene repair 96%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.