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Review
, 50 (2), 81-99

On the Origin and Functions of RNA-mediated Silencing: From Protists to Man

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Review

On the Origin and Functions of RNA-mediated Silencing: From Protists to Man

Heriberto Cerutti et al. Curr Genet.

Abstract

Double-stranded RNA has been shown to induce gene silencing in diverse eukaryotes and by a variety of pathways. We have examined the taxonomic distribution and the phylogenetic relationship of key components of the RNA interference (RNAi) machinery in members of five eukaryotic supergroups. On the basis of the parsimony principle, our analyses suggest that a relatively complex RNAi machinery was already present in the last common ancestor of eukaryotes and consisted, at a minimum, of one Argonaute-like polypeptide, one Piwi-like protein, one Dicer, and one RNA-dependent RNA polymerase. As proposed before, the ancestral (but non-essential) role of these components may have been in defense responses against genomic parasites such as transposable elements and viruses. From a mechanistic perspective, the RNAi machinery in the eukaryotic ancestor may have been capable of both small-RNA-guided transcript degradation as well as transcriptional repression, most likely through histone modifications. Both roles appear to be widespread among living eukaryotes and this diversification of function could account for the evolutionary conservation of duplicated Argonaute-Piwi proteins. In contrast, additional RNAi-mediated pathways such as RNA-directed DNA methylation, programmed genome rearrangements, meiotic silencing by unpaired DNA, and miRNA-mediated gene regulation may have evolved independently in specific lineages.

Figures

Fig. 1
Fig. 1
Domain architecture of Dicer-like proteins from species belonging to five eukaryotic supergroups. Protein sequences were examined for the presence of conserved domains by comparison with the SMART and PFAM databases and their diagrams are shown to scale. DEXDc DEAD-like helicase domain; HELIc helicase C-terminal domain; DUF283 DUF283 domain; PAZ PAZ domain; RNAseIII (a-b) RNaseIII domains a and b, DSRM Double-stranded RNA binding domain. The DEXDc and HELIc motifs are referred to as the SFII RNA helicase domain in the text. At Dcl1 A. thaliana Dcl1 (NP_171612); Dd DDB0202199 D. discoideum DDB0202199 (EAL73658); Gi Dcl1 G. intestinalis Dcl1 (AAO17549); Hs Dcr1 H. sapiens Dcr1 (NP_803187); Ps Dcl1 P. sojae Dcl1 (v1_C_860007 at http://www.genome.jgi-psf.org/sojae1/sojae1.home.html); Spo Dcr1 S. pombe Dcr1 (Q09884); Tt Dcr2 T. thermophila Dcr2 (BAD34723)
Fig. 2
Fig. 2
Neighbor-Joining tree showing the phylogenetic relationship among Argonaute-Piwi proteins. Sequences corresponding to the PAZ and PIWI domains were aligned using the ClustalX program and the tree was drawn using the MEGA 3.1 program. Numbers indicate bootstrap values, as percentage, based on 1,000 pseudoreplicates (only values > 60% are shown). The Ago-like and Piwi-like protein subclasses are shown to the right of the tree. Species are designated by a two-letter abbreviation preceding the name of each protein: Ag A. gambiae; At A. thaliana; An A. nidulans; Ce C. elegans; Cr C. reinhardtii; Ci C. intestinalis; Dd D. discoideum; Dm D. melanogaster; Eh E. histolytica; Gi G. intestinalis; Hs H. sapiens; Nc N. crassa; Os O. sativa; Pt P. tetraurelia; Ps P. sojae; Spo S. pombe; Sp S. purpuratus; Tt T. thermophila; and Tb T. brucei. Accession numbers of proteins used to draw the tree: Ag Ago1 EAA00062; Ag Ago2 EAL41436; Ag Piwi EAA05900; At Ago1 AAC18440; At Ago2 NP_174413; At Ago3 NP_174414; At Ago4 NP_565633; At Ago5 NP_850110; At Ago6 NP_180853; At Ago7(ZIP) NP_177103; At Ago8 NP_197602; At Ago9 NP_197613; At Ago10(PNH) CAA11429; An AN1519 EAA63775; Ce Alg1 NP_510322; Ce Alg2 NP_871992; Ce C01G5 AAB37734; Ce D2030 CAA98113; Ce Ppw1 NP_740835; Ce Ppw2 AAF60414; Ce Rde1 NP_741611; Ce R04A9 NP_508092; Ce T23D8 NP_492643; Ce ZK757 CAB54247; Cr Ago1 v2_C_130206*; Cr Ago2 v2_1200017*; Ci Ago1 C_chr_ 02q000291*; Dd AgnA EAL69296; Dd AgnB EAL62204; Dd AgnC EAL71514; Dd AgnE EAL62770; Dd DDB0218341 EAL66399; Dm Ago1 BAA88078; Dm Ago2 Q9VUQ5; Dm Aub CAA64320; Dm Piwi Q9VKM1; Eh EAL51127 EAL51127; Gi GLP_170_185618_188320 XP_779885; Hs Ago1(eIF2C-1) AAH63275; Hs Ago2(eIF2C-2) AAL76093; Hs Ago3(eIF2C-3) BAB14262; Hs Ago4(eIF2C-4) BAB13393; Hs Hiwi AAC97371; Nc Qde2 AAF43641; Nc Sms2 AAN32951; Os Ago701 XP_468547; Os Ago702 BAB96813; Os Ago703 NP_912975; Os Ago704 XP_478040; Os Ago705 AL606693; Os Ago706 NP_909924; Os Ago707 AP005750; Os Ago708 XP_473529; Os Ago709 XP_473887; Os Ago710 XP_469312; Os Ago711 AP004188; Os Ago712 XP_476934; Os Ago713 XP_473888; Os Ago714 XP_468898; Os Ago715 XP_477327; Os Ago716 XP_464271; Os Ago717 XP_469311; Os Ago719 AP000836; Pt Ptiwi05 CAI44468; Pt Ptiwi10 CAI39070; Pt Ptiwi13 CAI39067; Pt Ptiwi15 CAI39065; Ps AgoL1 v1_C_580101*; Ps AgoL2 v1_C_1000004*; Spo Ago1 O74957; Sp Ago1 XP_782278; Sp Seawi AAG42533; Tt Twi1p AAM77972; Tt Twi2p AAQ74967; Tb Ago1 AAR10810. *Accession numbers according to the annotated draft genomes of C. reinhardtii, C. intestinalis, or P. sojae at http://www.genome.jgi-psf.org/euk_cur1.html
Fig. 3
Fig. 3
Phylogenetic tree of Dicer-like proteins. Sequences corresponding to the RNaseIIIa and b domains were aligned using the ClustalX program and a Neighbor-Joining tree was constructed and drawn using MEGA 3.1. Numbers show bootstrap values, as percentage, based on 1,000 pseudoreplicates (only values > 60% are shown). The Dicer-like, eubacterial RNaseIII, and Drosha-like protein subclasses are indicated to the right of the tree. Species are designated by a two-letter abbreviation preceding the name of each protein, as shown in the legend to Fig. 2 but also including: Aa Aedes aegypti; Ec Escherichia coli; and St Streptococcus thermophilus. Accession numbers of proteins used to draw the tree: Aa Dcr1 AAW48724; Aa Dcr2 AAW48725; Ag Dcr1 AAO73809; Ag Dcr2 EAA00264; Ag Drsh1 EAL39656; At Dcl1 NP_171612; At Dcl2 NP_566199; At Dcl3 NP_189978; At Dcl4 NP_197532; An AN3189 XP_660793; Ce Dcr1 P34529; Ce Drsh1 NP_492599; Cr Dcl1 v2_C_130110 (at http://www.genome.jgi-psf.org/Chlre3/Chlre3.home.html); Dd DDB0202199 EAL73658; Dd DrnA EAL70472; Dm Dcr1 Q9VCU9; Dm Dcr2 BAB69959; Dm Drsh1 AAD31170; Ec RNaseIII AAC75620; Gi Dcl1 AAO17549; Hs Dcr1 NP_803187; Hs Drsh1 Q9NRR4; Nc Dcl2 CAB91758; Nc Sms3 XP_328976; Os Dcl701 NP_912466; Os Dcl702 XP_463595; Os Dcl703 NP_922059; Os Dcl704 XP_473129; Os Dcl705 XP_463068; Pt Dcr1 CAI44479; Spo Dcr1 Q09884; St RNaseIII AAV62839; Sp Dcr1 XP_790894; Sp Drsh1 XP_790161; Tt Dcr1 BAD34724; Tt Dcr2 BAD34723
Fig. 4
Fig. 4
Phylogenetic tree of eukaryotic RNA-dependent RNA polymerases. An alignment of sequences corresponding to the RdRP domain was used to construct a Neighbor-Joining tree and its robustness was assessed by a bootstrap test based on 1,000 pseudoreplicates. Bootstrap values higher than 60% are shown on the nodes of the tree. Species are indicated by a two-letter abbreviation preceding the name of each protein, as shown in the legend to Fig. 2. Accession numbers of proteins used to draw the tree: At Rdr1 NP_172932; At Rdr2 NP_192851; At Rdr3 NP_179581; At Rdr4 NP_179582; At Rdr5 NP_179583; At Rdr6(SDE1) NP_190519; An AN2717 XP_660321; An AN4790 XP_662394; Ce Ego1 NP_492132; Ce Rrf1 AAF80368; Ce Rrf2 NP_493057; Ce Rrf3 NP_495713; Dd DosA AAD29638; Dd RrpB CAC41975; Eh Rdrp1 EAL45936; Gi Rdrp AAK97084; Nc Qde1 CAB42634; Nc Rrp3 CAD70515; Nc Sad1 AAK31733; Os Rdr701 NP_918046; Os Rdr702 NP_913147; Os Rdr703 NP_913148; Os Rdr704 AP004880; Os Rdr705 XP_472792; Pt Rdrp1 CAI39057; Pt Rdrp2 CAI39056; Spo Rdp1 O14227

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