Table 1.
Coelimination and codivergence of functionally linked genes in S. cerevisiae*
| Protein function and representative in S. pombe† | Domain architecture‡ | L/D§ | Comments |
|---|---|---|---|
| Posttranscriptional gene
silencing/mRNA stability and modification | |||
| RNA-dependent RNA polymerase (3169081) | RNA-dependent RNA polymerase | L | Involved in posttranscriptional silencing in plants and Neurospora |
| Argonaute/eIF2C (2330856) | Argonaute | L | Involved in RNA I-mediated silencing in C. elegans |
| RNA helicase-nuclease (1351642) | SFII-Helicase+2*RNASEIII | L | Ortholog of plant protein carpel factory involved in regulation of cell proliferation |
| RNAse PH family protein (1723274) | RNAse PH | L | |
| 3′ → 5′ exonuclease (4007797) | 3′ → 5′ exonuclease | L | Ortholog of the deadenylating nuclease involved in RNA decay |
| Inactive RNA helicase (4160338) | SFI-helicase | L | Ortholog of the animal protein Aquarius, a superfamily I helicase with disrupted catalytic motifs (L.A. and E.V.K., unpublished data) |
| RNA helicase (6048290) | SFI-helicase | L | |
| Zn-knuckle RNA-binding protein (3738189) | 5*Zn-knuckle | L | A paralog of the clipper/polyadenylation complex subunit CPSF30 |
| NMD2 (2388907) | 2*NIC domain | D | An adapter protein in the nonsense-mediated RNA decay pathway¶ |
| NAM7 helicase (3581879) | SFI-helicase | D | Helicase involved in nonsense-mediated RNA decay¶ |
| Spliceosome | |||
| U2AF, 23-kDa subunit (6136086) | Zn-knuckle+RRM+Zn-knuckle | L | RNA-binding protein of the U2 snRNP |
| U2AF, 59 kDa (549144) | RRM | L | RNA-binding protein of the U2 snRNP |
| U5 snRNP, 40-kDa subunit (4495124) | WD40 protein | L | Predicted adapter-mediating protein–protein interactions |
| U2 B" protein (3169094) | 2RRM* | L | Predicted RNA-binding protein |
| Component of U1 RNP Yhc1p (3006184) | C2H2 finger domain | D | Predicted RNA-binding protein |
| PRP21 ortholog (2414602) | SWAP domain | D | Along with PRP9, activates U2 snRNP to bind pre-mRNA |
| PRP9 ortholog (3135996) | C2H2 finger domain | D | Predicted RNA-binding protein |
| PRP39 (3169096) | TPR repeats | D | Predicted adapter mediating protein–protein interactions |
| Predicted RNA-binding protein (2104448) | C4+C2H2+RRM+G-patch | L | Multiple RNA-binding domains |
| Predicted RNA-binding protein (2879872) | RRM+PWI | L | Predicted RNA binding with spliceosome-associated PWI domain |
| Predicted RNA-binding protein (3810835) | NTF2+RRM | L | Could be involved in the transport of pre-mRNA base on the NTF2 domain |
| Predicted RNA-binding protein (1351664) | 2*KH | L | |
| Predicted RNA-binding protein (6066740) | PWI | L | PWI domain is present in several splicing factors and could bind RNA |
| Predicted RNA-binding protein (2467274) | RRM | D | |
| Chromatin/nuclear structure-associated proteins | |||
| Clr4 (3334847) | Chromodomain+SET | L | Predicted methyltransferase involved in transcriptional silencing |
| SWI6 (730857) | Chromodomain | L | Heterochromatinic chromodomain protein ortholog |
| Inactivated cytosine-specific DNA methyltransferase (730347) | SAM-binding methylase domain | L | Apparently inactive ortholog of animal silencing-associated methylases of animals |
| MLO2 (2498563) | PHD finger | L | Affects chromosome segregation when overexpressed |
| BAF53 homolog (1351610) | Actin | L | SNF/SWI complex-associated Actin |
| NASP ortholog (5830515) | NASP domain | L | Member of a highly conserved family of Histone-binding proteins |
| Nuclear matrix protein p84 ortholog (6562903) | Unique domain | L | The vertebrate ortholog binds Retinoblastoma protein |
| ASH2 ortholog (3080533) | SPRY+PHD | L | Orthologous Drosophila protein ASH2 is a part of the chromatin-associate Trithorax complex |
| Predicted chromatin-associated, DNA-binding protein (5706512) | PHD+JOR+PHD | L | Homolog of human XE169 protein; the JOR domain may possess an as yet unknown enzymatic activity |
| Predicted chromatin protein (5441491) | SWI3+Rossmann-fold oxidase +HMG1 | L | Novel configuration of domains; may be a hitherto unexplored, chromatin-associated, NAD/FAD-dependent enzyme |
| Predicted adenine-specific DNA methylase (1175468) | SAM-binding methylase domain | L | Belongs to the Kar4/Ime4 family of adenine methylases; could be involved in a novel pathway of transcription/chromatin structure regulation |
| Predicted chromatin protein (2370493) | JOR | L | May possess an as yet unknown enzymatic activity |
| Predicted chromatin protein (1351640) | SKI/SNW | D | Homolog of the animal SKIP protein involved in transcriptional regulation |
| DNA repair/replication/damaged DNA-associated checkpoints | |||
| Hus1 (3219811) | PCNA clamp | L | Component of the damaged DNA-sensing complex |
| RAD9 (131816) | PCNA clamp | L | Component of the damaged DNA-sensing complex |
| RAD17 (1709996) | Clamp loader (AAA+) ATPase | D | Component of the damaged DNA-sensing complex |
| DINB1 ortholog (4038629) | DNA polymerase V+2HhH* | L | Translesion DNA repair polymerase |
| AlkB ortholog (3080529) | AlkB | L | Predicted hydrolytic enzyme involved in alkylated DNA repair |
| G/T mismatch-specific thymine DNA glycosylase (3915098) | DNA glycosylase | L | |
| Endonuclease V (1723511) | EndoV | L | Endonuclease involved in DNA repair |
| Telomerase (2340169) | Reverse transcriptase | D | Telomere maintenance |
| Ciliate-type telomere-binding protein (7491013) | OB-fold domain-containing single-stranded DNA-binding protein | L | Telomere maintenance |
| Replication protein A (2498845) | OB-fold | D | Replication initiation |
| CDC18 (1168808) | (AAA+) ATPase | D | S phase–mitosis coupling |
| ORC1 (1709487) | BAM+(AAA+) ATPase | D | ATPase subunit of the origin-recognition complex |
| ORC3 Latheo (6224782) | ORC3 | D | Origin recognition complex subunit |
| ORC5 (6093628) | Inactive AAA+ ATPase | D | ATP-binding but not hydrolyzing origin recognition complex subunit |
| TRF4/5 family protein (3219960) | Polβ family nucleotidyltransferase | L | Predicted to be involved in DNA repair in conjunction with topoisomerase I |
| Terminal Nucleotidyl transferase (1175369) | polβ family nucleotidyl transferase | L | Ortholog of vertebrate terminal deoxynucleotidyl transferases |
| Predicted DNAase (3417434) | SAP+3′ → 5′ nuclease (KapD family) | L | Predicted to localize to regions of active chromatin |
| Predicted A/G mismatch-specific DNA glycosylase (1723233) | DNA glycosylase+HhH | L | |
| Signalosome/eIF3/proteasome | |||
| EIF3 p66 (4056551) | Unique domain | L | |
| EIF3 p48/int6 (4160345) | PINT | L | Component of both signalosome and eIF3 |
| GPS1 ortholog (3873540) | PINT | L | Negative regulator of AP-1 transcription |
| EIF3 p40 (6014439) | PAD1/JAB1 | L | Component of both signalosome and eIF3 |
| EIF3 p167 ortholog (3650404) | Unique domain | D | eIF3 component |
| EIF3 Tif31p (6491837) | Unique domain | D | eIF3 component |
| Predicted signalosome subunit (5731945) | PINT | L | |
| Predicted signalosome subunit (2414596) | PINT | L | |
| Predicted signalosome subunit (3327876) | PINT | L | |
| Predicted signalosome subunit (2832888) | PAD1/JAB1 | L | |
| Protein folding, modification, and processing | |||
| BAG-2 homolog (3133105) | Ubiquitin | L | Ubiquitin-like lysine modification of proteins |
| Leucine aminopeptidase (1175415) | l-Aminopeptidase | L | Exoproteolytic processing of proteins |
| Peptidylprolyl isomerase (3169061) | WD40+cyclophilin | L | |
| Peptidylprolyl isomerase (1351676) | U-box+cyclophilin | L | A chaperone potentially involved in the assembly of proteosome-type complexes |
| Peptidylprolyl isomerase (5738526) | Cyclophilin+RRM | L | A chaperone potentially involved in the spliceosome assembly |
The cases in which experimental evidence for a role in the given pathway or complex exists for the particular S. pombe protein or its ortholog from another organism are shown in boldface. The remaining (not boldfaced) proteins in each category are predicted to belong to the same pathway or complex on the basis of coelimination and codivergence combined with analysis of domain composition.
GenBank identifiers (GI numbers) for the respective S. pombe proteins are given in parentheses.
Domains are shown consecutively from the N terminus to the C terminus. Known and predicted nucleic acid-binding domains: RRM (RNA recognition motif), Zn-knuckle, C4, C2H2 and PHD Zn-fingers, G-patch, HhH (helix–hairpin–helix), SAP (SAF-A/B, Acinus, and PIAS), SPRY (SplA ryanodine receptor domain), SWAP (suppressor of white apricot), OB (oligomer-binding)-fold, PWI (PWI motif-containing domain); protein–protein interaction adapter domains: WD40, TPR (tetratricopeptide) repeats, BAM (bromo-associated motif), NIC (NMD2, eIF4G, CBP80), PINT (proteasomal subunits, Int-6, Nip-1, Trip-15), PAD1/JAB1 (Jun activation domain binding), SKI/SNW (domain found in SKIP/SnwA proteins), PCNA (proliferating cell nuclear antigen), U (ubiquitination) box. Other, including enzymatic, domains include SFI, SFII [superfamily I and II (helicases)], JOR (Jumonji-related), AAA+ (a superfamily of ATPases including the classic AAA proteins), EndoV (endonuclease V domain), and NTF2 (nuclear transport factor 2 domain). For detailed information on most of these domains, see the SMART web site, http://smart.embl-heidelberg.de/.
L, apparent gene loss; D, gene divergence.
The correlation between the divergence of these genes with the loss of the PTGS suggests the possibility of a functional connection between the latter and nonsense-mediated mRNA decay.