Table 1 |.
Machineries of non-coding RNA surveillance
| Activity | Factor | Main function | Main subunits: related diseases |
|---|---|---|---|
| Endonuclease | RNase H1 | Mitochondrial RNA processing, DNA replication | – |
| RNase H2 | Nuclear R-loop processing, ribonucleotide excision repair | Aicardi-Goutieres syndrome150,151 | |
| Integrator complex | Transcription termination | – | |
| 3′−5′ Exonuclease | RNA exosome complex | Nuclear and cytoplasmic RNA degradation, R-loop processing | DIS3: multiple myeloma156; EXOSC2: retinitis pigmentosa140; EXOSC3: pontocerebellar hypoplasia type 1, spinal motor neuron disease141–144; EXOSC8: cerebellar and corpus callosum hypoplasia, spinal motor neuron disease139; EXOSC10 |
| PARN | Po1y(A)-specific ribonuclease | Dyskeratosis congenita177,178; familial pulmonary fibrosis179 | |
| 5′−3′ Exonuclease | XRN1 | Cytoplasmic RNA degradation | – |
| XRN2 | Nuclear RNA degradation, transcription termination | – | |
| Helicase | MTR4 | Processing double-stranded RNA and RNA–DNA hybrids | – |
| Senataxin (SETX) | R-loop processing, transcription termination | Ataxia with oculomotor apraxia type 2 (REF146); amyotrophic lateral sclerosis147 | |
| Aquarius | R-loop processing | – | |
| DDX1 | R-loop processing, G-quadruplex processing | – | |
| DHX9 | R-loop processing, G-quadruplex processing | – | |
| DDX5 | R-loop resolution with XRN2 | – | |
| DDX19 | RNA export, R-loop processing | – | |
| DDX21 | R-loop processing | – | |
| DDX23 | R-loop processing | Adenoid cystic carcinoma88 | |
| Cofactors | NEXT complex | Nuclear cofactor of the RNA exosome, primarily targeting nascent transcripts | MTR4, RBM7: pontocerebellar hypoplasia type 1-like and spinal muscular atrophy145; ZCCHC8: familial pulmonary fibrosis180 |
| PAXT complex | Nuclear cofactor of the RNA exosome, targeting poly(A)-tailed transcripts | MTR4, PABPN1, ZFC3H1 |
DDX, DEAD-box; DHX, DEAH-box; EXOSC, exosome component; NEXT, nuclear exosome targeting; PABPN1, poly(A) binding protein nuclear 1; PARN, poly(A)-specific ribonuclease; PAXT, poly(A)-tail exosome targeting; RBM7, RNA-binding protein 7; RNase, ribonuclease; XRN, 5′–3′ exoribonuclease; ZCCHC8, zinc finger CCHC domain-containing protein 8; ZFC3H1, zinc finger C3H1 domain-containing protein.