Table 1.
The proteins involved in miRNA-mediated mechanisms of gene expression regulation and their interactors
| Protein | Role | Interactors (interacting protein domain) | miRNA-mediated mechanism of gene expression regulation | References |
|---|---|---|---|---|
| Ago1–4 (Argonaute) | Core component of miRISC, miRNA binding | TNRC6 (PABC domain), FMRP, Imp8, HuR | Translation inhibition or upregulation, transcript deadenylation and decapping | [59, 82, 85] |
| TNRC6A–C (GW182, GW-repeat containing protein) | Core component of miRISC and P/GW-bodies; linker between PABP and deadenylases | Ago (GW/WG-repeats), PABP (PAM2 domain), EDD (PAM2 domain), PAN3 (CIM2 region), | Translation inhibition or upregulation, transcript deadenylation and decapping | [196, 201, 262, 263] |
| TNR6A | Ago2-navigator protein | CNOT1 (CIM1/CIM2 region), Exp1 (NES) | Gene silencing in the nucleus | [245] |
| PABPA–C (polyA-binding protein) | Binding to polyA tail of transcript; interaction with initiation factors | TNRC6 (PABC domain), PAN3 (PABC domain) | Translation inhibition, transcript deadenylation | [264] |
| PAN2–PAN3 complex: | Initial transcript deadenylation | |||
| PAN2 (polyA nuclease) | Nuclease activity | PAN3 | [228] | |
| PAN3 | Binding to other proteins | PABP (PAM2 domain), TNRC6 (PAM2 domain), PAN2 | [201, 232] | |
| Multisubunit CCR4-NOT complex: | Transcript deadenylation | |||
| CNOT1 | Scaffold for CCR4-NOT complex | TNRC6, Caf1, CNOT4, CNOT2/3, CNOT 9/10 | [200–202] | |
| Caf1a/b (CNOT7/8) | Deadenylase subunit | CNOT1 | [233] | |
| Ccr4a/b (CNOT6/6L) | Deadenylase subunit | CNOT1, Caf1 (leucin-rich region, LRR) | [228, 265, 266] | |
| Tob | Association of CCR4-NOT | Caf1, PABP (PAM2 domain), EDD | Transcript deadenylation | [264] |
| DCP1-DCP2 complex: | Transcript decapping | |||
| DCP1 (decapping protein) | DCP2 activator | DCP2 | [239, 267] | |
| DCP2 | Decapping subunit | DCP1, RCK/p54, LSm4, PNRC2 | [239, 267, 268] | |
| RCK/p54 or DDX6 (DEAD-box helicase) | DCP2 activator; responsibility for the P-body localization of DCP1-DCP2 | DCP2, EDC3, Pat1, EDD | Cap-dependent translation repression, transcript decapping | [239, 269, 270] |
|
EDC4 EDC3 |
Association between DCP1 and DCP2; stimulation of decapping | DCP2, RCK/p54 | Transcript decapping | [270] |
| XRN1 | 5′-3′ exoribonuclease activity | Pat1 | Transcript degradation | [271] |
| FMRP | Stress granule component | Ago1, Ago2 | Translation regulation | [221, 244, 272, 273] |
| LSm4 | P-body component, decapping activator | DCP2 | Transcript degradation | [244] |
| PNRC2 | Synergy with DCP1, decapping stimulation | DCP2 | Transcript decapping | [267, 274] |
| Pat1 | DCP2 activator, linker between deadenylation and decapping, induce the formation of P-bodies | DCP2, XRN1, RCK/p54 | Transcript decapping | [271] |
| EDD | E3 ubiquitin ligase | TNRC6 (PABC domain), RCK/p54, Tob | Translation inhibition and transcript deadenylation | [275] |
| Imp8 (Importin-8) | Transport to the nucleus | Ago | Translation inhibition | [244] |
| Exp1 (Exportin-1) | Transport of TNRC6A from nucleus | TNRC6 | Gene silencing in the nucleus | [245] |
| HuR | Binding to AU-rich elements (ARE-binding site) by three RRM (RNA recognition motifs) | HuR oligomerization | HuR-mediated derepression of miRNA-mediated gene expression; HuR-stimulated miRNA-mediated gene silencing | [223, 276, 277] |