Table 1.
An overview of key enzymes and factors involved in eukaryotic mRNA decay
| Protein name | Full name | Function |
|---|---|---|
| Deadenylation | ||
| PAN2 | Poly(A)-nuclease deadenylation subunit 2 | Enzymatically active subunit of the PAN2/3 complex that is responsible for the preliminary poly(A) trimming |
| PAN3 | Poly(A)-nuclease deadenylation subunit 3 | Cofactor and regulatory subunit of the PAN2/3 complex that is responsible for the preliminary poly(A) trimming |
| CNOT6 (CCR4) | CCR4-NOT complex subunit 6 | 3′ to 5′ exonuclease that is the major catalytically active component of the CCR4-NOT complex that performs most of mRNA deadenylation |
| CNOT1 (NOT1) | CCR4-NOT complex subunit 1 | Scaffolding component of the CCR4-NOT deadenylation complex |
| CNOT7 (CAF1/POP2) | CCR4-NOT complex subunit 7 | Minor deadenylase in the CCR4-NOT complex; its function is somewhat redundant to CNOT6 (CCR4) |
| PARN | Poly(A)-specific ribonuclease | 3′ to 5′ exoribonuclease that interacts with the 5′ cap and preferentially degrades poly(A) tails |
| Decapping | ||
| DCP2 | Decapping protein 2 | Catalytically active component of the decapping complex that removes the 5′ mRNA cap through hydrolysis reaction |
| DCP1 | Decapping protein 1 | Primary cofactor for DCP2; it enhances hydrolysis activity of DCP2 and interacts with other proteins to recruit DCP1/2 complex to mRNA substrates |
| PATL1 (Pat1) | PAT1 homolog protein 1 | Scaffolding protein in deadenylation-dependent decapping; it connects decapping and deadenylation machinery |
| Lsm1-7 | Sm-like protein complex | Identifies and associates with deadenylated transcripts; it interacts with PALT1 to recruit the DCP1/2 complex |
| DDX6 (Dhh1) | DEAD-box helicase 6 | RNA helicase enzyme that interacts with other decapping factors and is thought to remodel the transcript to promote efficient decapping complex assembly |
| LSM14 (Scd6) | Sm-like protein 14 | Serve as a scaffold for assembly and activation of DCP1/2 complex |
| EDC1,2,3 | Enhancer of mRNA-decapping proteins | Serve as a scaffold for assembly and activation of DCP1/2 complex |
| 5′ to 3′ decay | ||
| XRN1 | 5′-3′ exoribonuclease | Major 5′ to 3′ exoribonuclease that preferentially degrades RNAs with a 5′ monophosphate |
| 3′ to 5′ decay | ||
| Exo9 | Exosome complex (9-subunit) | The core of the exosome that consists of nine different protein subunits |
| RRP44 | Exosome complex exonuclease RRP44 | Catalytically active subunit of the exosome |
| SKI7 | Superkiller protein 7 | GTP-binding protein that recruits the exosome to nonpoly(A) mRNAs; it is involved in several, including NSD, NMD, and antiviral activity |
| DCPS | Decapping scavenger enzyme | Catalyzes the cleavage of the residual 5′ cap from short oligonucleotide sequence following 3′ to 5′ decay |
| DIS3L2 | DIS3-like exonuclease 2 | 3′ to 5′ exoribonuclease that specifically recognizes polyuridylated RNAs and mediates their degradation |
| TUT4/7 | Terminal uridyltransferase 4/7 | Uridyltransferases that mediate terminal uridylation of mRNAs with short poly(A) tails, thus facilitating their degradation |
| Endonucleolytic decay | ||
| MCPIP1 | Regnase 1/endoribonuclease ZC3H12A | Endonuclease that facilitates mRNA decay and is linked to various biological functions, including immune and inflammatory responses |
| HRSP12 | Heat-responsive protein 12 | Protein with endonuclease activity that is involved in activity and formation of the GMD complex |
| IRE-1 | Inositol-requiring enzyme 1 | Endonuclease that targets a series of mRNAs connected to several cellular processes |
| RNase L | Ribonuclease L or ribonuclease 4 | Inducible endoribonuclease associated with antiviral response |
mRNA, Messenger RNA; NSD, nonstop decay; NMD, nonsense-mediated decay; GMD, glucocorticoid receptor-mediated decay.