| RNA silencing suppressor p19 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Theprotein dimer formed by two p19 molecules. Each monomer is colored fromN-terminus (blue) toC-terminus (red) to illustrate the end-to-end orientation of the dimer. The dotted gray line in the center highlights the dimer interface. FromPDB:1R9F.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | Tombus_p19 | ||||||||
| Pfam | PF03220 | ||||||||
| InterPro | IPR004905 | ||||||||
| |||||||||
RNA silencing suppressor p19 (also known asTombusvirus P19 core protein and19 kDa symptom severity modulator) is aprotein expressed from theORF4gene in thegenome oftombusviruses. Theseviruses arepositive-sense single-stranded RNA viruses that infectplant cells, in whichRNA silencing forms a widespread and robust antiviral defense system. The p19 protein serves as a counter-defense strategy, specifically binding the 19- to 21-nucleotidedouble-stranded RNAs that function assmall interfering RNA (siRNA) in the RNA silencing system. By sequestering siRNA, p19 suppresses RNA silencing and promotes viral proliferation.[1][2][3] The p19 protein is considered a significantvirulence factor[4] and a component of anevolutionary arms race between plants and theirpathogens.[5]
The p19 protein received its name from its size, being approximately 19kilodaltons. It forms a functionalhomodimer. Thecrystal structures are available of p19 proteins from thetomato bushy stunt virus[1] andCarnation Italian ringspot virus;[2] the protein consists of a novelprotein fold and exemplifies a previously unknown mechanism for bindingRNA, using a binding surface formed by abeta sheet and flanked byalpha helices to interact with double-stranded RNAs of around 21nucleotides in length in a non-sequence-specific manner.[1][2][7]
The p19 protein binds to double-stranded RNAs that function asshort interfering RNA (siRNA) and is specialized for the 21-nucleotide product of the enzymeDCL4 (a member of a family of plant enzymes with homology toDicer).[7] By binding to siRNA, p19 sequesters these species and prevents them from interacting with theRNA-induced silencing complex (RISC), aprotein complex that mediates the antiviralRNA silencing mechanism in the cell.
The p19 protein is also capable of binding tomicroRNA molecules that are endogenous to the host cell, as well as the siRNAs that are ultimately derived from the virus's own genome. Notably, an exception to this pattern is p19's inefficiency in interacting with the microRNAmiR-168, a regulatorynon-coding RNA thatrepresses expression ofargonaute-1 (AGO1). The AGO1 protein is required for RNA silencing, thus selectively sparing its repressor from p19's general sequestration of miRNA has the effect of reducing cellular AGO1 levels and is an additional mechanism by which p19 inhibits silencing.[5][8] The two mechanisms are independent of one another and can be selectively abrogated bymutations.[9]
The gene encoding the p19 protein is an example of anoverprinted gene, a genomic arrangement common in viruses in which multiple genes are encoded by the same portion of the genome read in alternatereading frames.[10][11] Theopen reading frame ORF4, which encodes p19, is completely contained within the open reading frame of another gene, which is designated ORF3 and encodes themovement protein p22. Both genes, and their relative positions, are conserved within the tombusvirus family.[4][11] P19 is thought to have originatedde novo in this lineage.[11][12]
Sequestration of dsRNA is a common viral counter-defense strategy against RNA silencing, evolved in a form ofevolutionary arms race between virus and host.[5] The p19 protein is not unique in this role; in an example ofconvergent evolution, this strategy appears to have evolved at least three times in distinct viral lineages using proteins with distinct structures and physical means of binding RNA.[3][13][14]
Thetomato bushy stunt virus, which is thetype species of thetombusvirus family, is a long-standingmodel system for the study ofplant viruses. The open reading frame encoding p19 was originally discovered in the late 1980s when the virus's genome was sequenced; it was subsequently demonstrated that the predicted protein was indeed expressed from the gene, although its role in promoting virulence and infectivity was initially underappreciated. Following the elucidation of its role as a suppressor of RNA silencing, p19 has also been used as a tool inmolecular biology research on RNA silencing,RNA interference, and related processes.[4][6]