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RNA binding of Hfq monomers promotes RelA-mediated hexamerization in a limiting Hfq environment

Pallabi Basu, Maya Elgrably-Weiss, Fouad Hassouna, Manoj Kumar, Reuven Wiener and Shoshy Altuvia ()
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Pallabi Basu: The Hebrew University, Hadassah Medical School
Maya Elgrably-Weiss: The Hebrew University, Hadassah Medical School
Fouad Hassouna: The Hebrew University, Hadassah Medical School
Manoj Kumar: The Hebrew University, Hadassah Medical School
Reuven Wiener: The Hebrew University, Hadassah Medical School
Shoshy Altuvia: The Hebrew University, Hadassah Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract The RNA chaperone Hfq, acting as a hexamer, is a known mediator of post-transcriptional regulation, expediting basepairing between small RNAs (sRNAs) and their target mRNAs. However, the intricate details associated with Hfq-RNA biogenesis are still unclear. Previously, we reported that the stringent response regulator, RelA, is a functional partner of Hfq that facilitates Hfq-mediated sRNA–mRNA regulation in vivo and induces Hfq hexamerization in vitro. Here we show that RelA-mediated Hfq hexamerization requires an initial binding of RNA, preferably sRNA to Hfq monomers. By interacting with a Shine–Dalgarno-like sequence (GGAG) in the sRNA, RelA stabilizes the initially unstable complex of RNA bound-Hfq monomer, enabling the attachment of more Hfq subunits to form a functional hexamer. Overall, our study showing that RNA binding to Hfq monomers is at the heart of RelA-mediated Hfq hexamerization, challenges the previous concept that only Hfq hexamers can bind RNA.

Date: 2021
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DOI: 10.1038/s41467-021-22553-x

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