In situ structures of rotavirus polymerase in action and mechanism of mRNA transcription and release.

Abstract:

:Transcribing and replicating a double-stranded genome require protein modules to unwind, transcribe/replicate nucleic acid substrates, and release products. Here we present in situ cryo-electron microscopy structures of rotavirus dsRNA-dependent RNA polymerase (RdRp) in two states pertaining to transcription. In addition to the previously discovered universal "hand-shaped" polymerase core domain shared by DNA polymerases and telomerases, our results show the function of N- and C-terminal domains of RdRp: the former opens the genome duplex to isolate the template strand; the latter splits the emerging template-transcript hybrid, guides genome reannealing to form a transcription bubble, and opens a capsid shell protein (CSP) to release the transcript. These two "helicase" domains also extensively interact with CSP, which has a switchable N-terminal helix that, like cellular transcriptional factors, either inhibits or promotes RdRp activity. The in situ structures of RdRp, CSP, and RNA in action inform mechanisms of not only transcription, but also replication.

journal_name

Nat Commun

journal_title

Nature communications

authors

Ding K,Celma CC,Zhang X,Chang T,Shen W,Atanasov I,Roy P,Zhou ZH

doi

10.1038/s41467-019-10236-7

subject

Has Abstract

pub_date

2019-05-17 00:00:00

pages

2216

issue

1

issn

2041-1723

pii

10.1038/s41467-019-10236-7

journal_volume

10

pub_type

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