PT  - JOURNAL ARTICLE
AU  - Arina V. Drobysheva
AU  - Sofia A. Panafidina
AU  - Matvei V. Kolesnik
AU  - Evgeny I. Klimuk
AU  - Leonid Minakhin
AU  - Maria V. Yakunina
AU  - Sergei Borukhov
AU  - Emelie Nilsson
AU  - Karin Holmfeldt
AU  - Natalya Yutin
AU  - Kira S. Makarova
AU  - Eugene V. Koonin
AU  - Konstantin V. Severinov
AU  - Petr G. Leiman
AU  - Maria L. Sokolova
TI  - Structure and function of virion RNA polymerase of crAss-like phage
AID  - 10.1101/2020.03.07.982082
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.07.982082
4099  - http://biorxiv.org/content/early/2020/03/08/2020.03.07.982082.short
4100  - http://biorxiv.org/content/early/2020/03/08/2020.03.07.982082.full
AB  - CrAss-like phages are a recently described family-level group of viruses that includes the most abundant virus in the human gut1,2. Genomes of all crAss-like phages encode a large virion-packaged protein2,3 that contains a DFDxD sequence motif, which forms the catalytic site in cellular multisubunit RNA polymerases (RNAPs)4. Using Cellulophaga baltica crAss-like phage phi14:2 as a model system, we show that this protein is a novel DNA-dependent RNAP that is translocated into the host cell along with the phage DNA and transcribes early phage genes. We determined the crystal structure of this 2,180-residue enzyme in a self-inhibited, likely pre-virion-packaged state. This conformation is attained with the help of a Cleft-blocking domain that interacts with the active site motif and occupies the RNA-DNA hybrid binding grove. Structurally, phi14:2 RNAP is most similar to eukaryotic RNAPs involved in RNA interference5,6, although most of phi14:2 RNAP structure (nearly 1,600 residues) maps to a new region of protein folding space. Considering the structural similarity, we propose that eukaryal RNA interference polymerases take their origin in a phage, which parallels the emergence of the mitochondrial transcription apparatus7.