Discovery and characterization of two new biochemical activities of RNA polymerase
Bacterial RNA polymerase was first purified and it’s DNA-dependent RNA synthesis activity reproduced in vitro several decades ago. However, many details of this large and complex enzyme remain to be described. remarkably, in 2006 Zenkin described two completely new and unexpected activities associated with RNA polymerase, which may have important biological functions. First, he described the mechanism of DNA replication primer synthesis by RNA polymerase that is used by number of plasmids and bacterial viruses instead of usual priming by primases. RNA polymerase was shown to possess the ability to initiate transcription at a specific site on a small hairpin of the single-stranded viral genome (rather than on usual double-stranded promoter). Synthesis on this template results in formation of completely novel kind of transcription elongation complex that serves as a priming complex for DNA polymerase. Second, Zenkin showed that RNA polymerase has a previously uncharacterized “proof-reading” function that contributes to the fidelity of transcription. The activity is assisted by incorrect transcript itself in a ribozyme-like manner. This latter work overturned the decades-old dogma that RNA synthesis differs fundamentally from DNA synthesis and is intrinsically error prone, due to the lack of proof reading activity.
Zenkin, N. and Severinov, K. 2004. The role of RNA polymerase sigma subunit in promoter-independent initiation of transcription. Proc. Natl. Acad Sci, USA 101, 4396-400.
Zenkin, N., Yuzenkova, Y. and Severinov, K. 2006. Transcript-assisted transcriptional proofreading. Science 313, 518-520.
Zenkin, N., Naryshkina, T., Kuznedelov, K. and Severinov, K. 2006. The mechanism of DNA primer synthesis by RNA polymerase. Nature 439, 617-620.