KSHV ORF57, a Protein of Many Faces
Abstract
:1. Introduction
2. The Primary Structure of ORF57 Protein
3. Expression and Localization of ORF57 Protein
4. Regulation of KSHV Gene Expression by ORF57
4.1. ORF57 Does Not Directly Export Viral RNAs
4.2. Stabilization of Viral Intronless Transcripts by ORF57
4.3. ORF57 Functions As a Viral Splicing Factor
4.4. ORF57 Promotes Protein Translation
4.5. Other Putative Functions of ORF57
5. Structural Determinants of ORF57 Function and Stability
5.1. ORF57 Secondary and Tertiary Structure
5.2. ORF57 Secondary Structure and Function
5.2.1. Roles of the ORF57 N-Terminal IDR in ORF57 Function
ORF57 cofactor | Cofactor function | Interaction region in ORF57 (aa) | Interaction region in cofactor (aa/Domain) | Proved direct interaction | Proposed function of interaction | Conserved interaction in homologues | Citation | |
---|---|---|---|---|---|---|---|---|
Cellular cofactors | ||||||||
Aly/REF | RNA-binding protein | 1–251 (181–215) | 103–163 (RRM) | + | RNA stability/Export (?) | + | [16,36] | |
CBP80 | RNA-binding protein | ND | ND | − | RNA stability/Export (?)/Translation | − | [45,56] | |
CKII α | Protein kinase | 181–455 | ND | + | Phopshorylation | + | [105] | |
CKII α' | Protein kinase | 387–455 | ND | + | Phopshorylation | + | [105] | |
CKII β | Protein kinase | 181–215 | 150-182 | + | Phopshorylation | + | [105] | |
hnRNP K | RNA-binding protein | 17–181/329–387 | 240–337 (KI) interactive domain | + | ? | + | [105] | |
hnRNP U | RNA-binding protein | 1–251 | ND | − | ? | − | [90] | |
Nup62 | Nucleoporin | ND | ND | − | ? | + | [106] | |
NXF1 | RNA export factor | ND | ND | − | Export (?) | + | [56] | |
OTT3 | RNA-binding protein | 1–251 | 488–890 (SPOC) | + | RNA stability/Polyadenylation | + | [38] | |
PABPC1 | RNA-binding protein | 1–251 | 1–370 (RRM1-4) | + | RNA stability | − | [56] | |
PCBP1 | RNA-binding protein | 179–205 | 48–96 (KH-I) | + | Translation | − | [74] | |
PYM | Scaffold protein | ND | ND | − | Translation | − | [75] | |
RBM15 | RNA-binding protein | 1–251 | 530–977 (SPOC) | + | RNA stability/Polyadenylation | + | [38] | |
SRSF1 | RNA-binding protein | ND | ND | − | RNA splicing | + | [20] | |
SRSF3 | RNA-binding protein | 1–251 | 1–83 (RRM) | − | RNA splicing | + | [31] | |
U snRNPs | Splicing factors | 1–251 | ND | − | RNA splicing | + | [20] | |
U2AF35 | RNA-binding protein | 1–251 | ND | − | RNA splicing | + | [20] | |
UAP56 | RNA-binding protein | ND | ND | − | Export (?) | + | [45] | |
UBE2O | Ubiqitin-conjugating enzyme E2O | 1-251 | ND | - | ? | - | [90] | |
UIF | RNA-binding protein | ND | ND | + | Export (?) | − | [50] | |
Viral cofactors | ||||||||
K-bZIP | Transcription factor | 96–215 | ND | + | ? | − | [85,86] | |
ORF23 | ? | ND | ND | + | ? | − | [86] | |
ORF50 | Transcription factor | ND | 1–518 (E3-LR) | + | Transactivation (?) | − | [83,84,86] | |
ORF52 | ? | ND | ND | + | ? | − | [86] | |
ORF57 | Posttranscriptional regulator | 251–455 | 251–455 | + | Self-interaction | + | [86,90,105] | |
ORF61 | Ribonucleotide reductase | ND | ND | + | ? | + | [86] | |
ORF63 | Tegument | ND | ND | + | ? | − | [86] | |
ORF67.5 | ? | ND | ND | + | ? | + | [86] | |
ORF68 | Glycoprotein | ND | ND | + | ? | + | [86] |
5.2.2. Phosphorylation of the ORF57 N-Terminal Domain
5.2.3. Homodimerization of ORF57 via Its C-Terminus
6. Regulation of ORF57 Stability by Phosphorylation and Homodimerization
7. Remarks and Perspectives
ORF57 RNA target | Expression stage | Coding potential | Identified MRE element | ORF57 activity toward the target | Citation |
---|---|---|---|---|---|
Viral RNA targets | |||||
vIL6 (K2) | E | Cytokine | MRE A/B | RNA stability/translation | [58] |
K4# | E | Chemokine | ND | ? | [58] |
K8 | E | Transcription factor (k-bZIP) | K8 intron 2 | Splicing | [20,31] |
K8.1# | L | Glycoprotein | ND | ? | [8] |
K9# | E | vIRF-1 | ND | ? | [58] |
K12# | L | Kaposin | ND | ? | [58] |
PAN | E | lncRNA | MRE I–III | RNA stability | [8,37,39,55] |
mPC# | L | Minor capsid protein | ND | ? | [9] |
ORF4 | E | Complement regulatory protein | ND | RNA stability (?) | [10] |
ORF6 | E | Single-stranded DNA binding protein | ND | RNA stability (?) | [10] |
ORF7# | L | Terminase subunit | ND | RNA stability (?) | [10] |
ORF8# | L | Glycoprotein B | ND | RNA stability (?) | [10] |
ORF9# | E | DNA polymerase | ND | ? | [9,10] |
ORF17# | L | Viral protease | ND | ? | [58] |
ORF47 | L | Glycoprotein | ND | RNA stability | [40,45] |
ORF50 | IE | Transcription factor (Rta) | ND | Splicing | [20,58] |
ORF52# | L | Tegument protein | ND | ? | [58] |
ORF56 | E | Primase | ND | RNA stability | [22,40] |
ORF59 | E | DNA polymerase processing factor | 5' MRE | RNA stability | [10,16,55,66] |
ORF60# | E | Ribonucleotide reductase subunit | ND | RNA stability (?) | [10] |
ORF61# | E | Ribonucleotide reductase subunit | ND | RNA stability (?) | [10] |
ORF73# | L | LANA | ND | ? | [58] |
Non-viral RNA targets | |||||
hIL6 | N/A | Cytokine | miR-608 binding site | Translation | [58] |
BPV-1 L1/L2 | N/A | Capsid proteins | SE4 | Splicing | [31] |
HPV16 L1/L2 | N/A | Capsid proteins | ESE | Splicing | [31] |
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Majerciak, V.; Zheng, Z.-M. KSHV ORF57, a Protein of Many Faces. Viruses 2015, 7, 604-633. https://doi.org/10.3390/v7020604
Majerciak V, Zheng Z-M. KSHV ORF57, a Protein of Many Faces. Viruses. 2015; 7(2):604-633. https://doi.org/10.3390/v7020604
Chicago/Turabian StyleMajerciak, Vladimir, and Zhi-Ming Zheng. 2015. "KSHV ORF57, a Protein of Many Faces" Viruses 7, no. 2: 604-633. https://doi.org/10.3390/v7020604