Table 2.
Factors involved in piRNA biogenesis in C. elegans
| Protein symbol | Type | Function | Phenotype of mutants | Human orthologue | Reference |
|---|---|---|---|---|---|
| FKH-3 | ForKHead transcription factor | Recognizing the Ruby motif; involved in type I 21 U-RNA biogenesis | N/A | N/A | [24, 45] |
| FKH-4 | ForKHead transcription factor | Recognizing the Ruby motif; involved in type I 21 U-RNA biogenesis | N/A | N/A | [24, 45] |
| FKH-5 | ForKHead transcription factor | Recognizing the Ruby motif; involved in type I 21 U-RNA biogenesis | N/A | N/A | [24, 45] |
| UNC-130 | UNCoordinated 130 | Binding to 21 U-RNA upstream regulatory sequence; required for piRNA transcription | N/A | FOXD4 | [59] |
| SNPC-4 | Small nuclear RNA activating protein complex | Binding to piRNA clusters; required for global piRNA expression | Lethal or sterile | SNAPC4 | [59] |
| PRDE-1 | Nuclear factor | Required for production of piRNA precursors from the Ruby motif; recruiting RNA polymerase II to the FKH motif | Mrt | N/A | [29, 60] |
| TOFU-3 | Twenty-One-u Fouled Ups | Required for the production or stability of 21 U-RNA precursors; a SUMO-related protease; interacting with HP1a and regulating its localization to pericentric heterochromatin | Mrt | N/A | [29, 47] |
| TOFU-4 | Twenty-One-u Fouled Ups | Required for the production or stability of 21 U-RNA precursors | Mrt | N/A | [29, 47] |
| TOFU-5 | Twenty-One-u Fouled Ups | Required for the production or stability of 21 U-RNA precursors; having a DNA-binding domain structurally related to that of Myb and found in various transcription regulatory factors | Lethal or sterile | N/A | [29, 47] |
| TBP-1 | TATA-box-binding protein | An additional factor required for TOFU-5 binding to piRNA clusters | N/A |
TBP TBPL2 |
[46] |
| PID-1 | piRNA-induced silencing-defective 1 | A potential nuclear import and export factor | Lethal | N/A | [56] |
| TOFU-1 | Twenty-One-u Fouled Ups | Required for precursor RNA processing after its production | Mrt | N/A | [29, 47] |
| TOFU-2 | Twenty-One-u Fouled Ups | Required for precursor RNA processing after its production | Mrt | N/A | [29, 47] |
| PARN-1 | RNase | Required for piRNA 3′ end trimming and having a 3′-to-5′ exo-RNase activity | Mrt | PARN PNLDC1 | [48] |
| TOFU-6 | Twenty-One-u Fouled Ups | A component of PETISCO; required for 21 U biogenesis | N/A | N/A | [29, 47] |
| TOFU-7 | Twenty-One-u Fouled Ups | Required for precursor RNA processing after its production | N/A | N/A | [29, 47] |
| HENN-1 | HEN methyltransferase 1 | Required for precursor RNA processing after its production | Sterile | HENMT1 | [61, 62] |
|
PID-3 (PICS-1) |
piRNA induced silencing defective | A component of PETISCO; required for 21 U biogenesis; interacting with 21 U-RNA precursor | Mes | N/A | [57] |
| ERH-2 | Enhancer of rudimentary homolog | A component of PETISCO; required for 21 U biogenesis; interacting with 21 U-RNA precursor | Mes | ERH | [57] |
| IFE-3 | Homologs of eIF4E | A component of PETISCO; required for 21 U biogenesis; binding to the 5′ cap of the 21 U precursor transcripts | Mes |
EIF4E EIF4E1B |
[57] |
| EGO-1 | Argonaute | RNA-dependent RNA polymerase | Sterile | N/A | [34, 63] |
| PRG-1 | PIWI protein | 21 U-RNA binding activity; combining with piRNA to form RISC | Mrt |
PIWIL1 PIWIL2 PIWIL3 PIWIL4 |
[19, 20] |
| CSR-1 | Argonaute | Self- and non-self-transcript discrimination | Mrt | N/A | [54, 55] |
| TOST-1 | Twenty-one U pathway antagonist | Inhibiting 21 U-driven silencing | Mes | N/A | [57] |
| EKL-1 | Enhancer of ksr-1 Lethality | Encoding a Tudor-domain protein required for RNAi; transgene silencing; transgene-mediated cosuppression in the germline | N/A | N/A | [47, 64] |
| DRH-3 | Dicer related helicase | A core component of the RdRp complex and essential for 22G-siRNA biogenesis | N/A | DHX58 | [65] |
| RRF-1 | Argonaute | RNA-dependent RNA polymerase | N/A | N/A | [66] |
| RDE-2 | RNAi defective | Interacting with MUT-7; required for efficient RNAi | N/A | N/A | [67] |
| MUT-7 | Mutator | Encoding a putative exoribonuclease; required for efficient RNAi | N/A | EXD3 | [67] |
| RDE-8 | RNAi defective | Cleaving target mRNAs to mediate silencing; generating mRNA fragments to serve as template for RdRp | N/A | N/A | [68] |
| MUT-16 | Mutator | Required for the accumulation of 22G-siRNA | N/A | N/A | [69] |
| SIMR-1 | Tudor domain protein | Mediating the production of secondary siRNAs by the mutator complex | Mrt | N/A | [70] |
| HRDE-1 | Nuclear Argonaute | Germline nuclear RNAi | Mrt | N/A | [71] |
| NRDE-3 | Nuclear Argonaute | Somatic nuclear RNAi | Mrt | N/A | [71] |
| MET-2 | H3K9me1/H3K9me2 methyltransferases | Required for 22G-siRNA formation | Mrt |
SETDB1 SETDB2 |
[72] |
| SET-25 | H3K9me3 methyltransferase | Heterochromatin maintenance, required for maintenance of piRNA-induced RNAi | N/A | N/A | [72] |
| SET-32 | H3K9me3 methyltransferase | Silencing establishment; required for multigenerational inheritance of environmental RNAi and piRNA silencing | Mrt | N/A | [73] |
| HPL-1 | Heterochromatin protein 1 | Binding with H3K9me2/H3K9me3; required for piRNA inducetion of heritable small RNAs | Sterile |
CBX1 CBX3 CBX5 |
[74] |
| HPL-2 | Heterochromatin protein 2 | Binding with H3K9me2/H3K9me3; required for piRNA inducetion of heritable small RNAs | Sterile | CBX3 | [75] |
| WAGO | Argonaute | Argonaute protein in C. elegans required for 22G-siRNA after RNA-dependent RNA polymerase activity | N/A |
AGO1 AGO2 AGO3 AGO4 |
[76] |
Abbreviations: Mrt mortal germline, Mes maternal-effect sterility, N/A not available