The structure of transcription termination factor Nrd1 reveals an original mode for GUAA recognition.

Transcription termination of non-coding RNAs is regulated in yeast by a complex of three RNA binding proteins: Nrd1, Nab3 and Sen1. Nrd1 is central in this process by interacting with Rbp1 of RNA polymerase II, Trf4 of TRAMP and GUAA/G terminator sequences. We lack structural data for the last of these binding events. We determined the structures of Nrd1 RNA binding domain and its complexes with three GUAA-containing RNAs, characterized RNA binding energetics and tested rationally designed mutants in vivo. The Nrd1 structure shows an RRM domain fused with a second α/β domain that we name split domain (SD), because it is formed by two non-consecutive segments at each side of the RRM. The GUAA interacts with both domains and with a pocket of water molecules, trapped between the two stacking adenines and the SD. Comprehensive binding studies demonstrate for the first time that Nrd1 has a slight preference for GUAA over GUAG and genetic and functional studies suggest that Nrd1 RNA binding domain might play further roles in non-coding RNAs transcription termination. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Elsa Franco-Echevarría, Noelia González-Polo, Silvia Zorrilla, Santiago Martínez-Lumbreras, Clara M Santiveri, Ramón Campos-Olivas, Mar Sánchez, Olga Calvo, Beatriz González, José Manuel Pérez-Cañadillas. The structure of transcription termination factor Nrd1 reveals an original mode for GUAA recognition. Nucleic acids research. 2017 Sep 29;45(17):10293-10305

PMID: 28973465

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