Drosophila nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of pumilio

Chase A. Weidmann, Chen Qiu, René M. Arvola, Tzu Fang Lou, Jordan Killingsworth, Zachary T. Campbell, Traci M. Tanaka Hall, Aaron Goldstrohm

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.

Original languageEnglish (US)
Article numbere17096
JournaleLife
Volume5
Issue numberAUGUST
DOIs
StatePublished - Aug 2 2016

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RNA-Binding Proteins
Clamping devices
Drosophila
RNA
Messenger RNA
Contraception
Gene expression
Crystal structure
Switches
Gene Expression

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Weidmann, C. A., Qiu, C., Arvola, R. M., Lou, T. F., Killingsworth, J., Campbell, Z. T., ... Goldstrohm, A. (2016). Drosophila nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of pumilio. eLife, 5(AUGUST), [e17096]. https://doi.org/10.7554/eLife.17096

Drosophila nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of pumilio. / Weidmann, Chase A.; Qiu, Chen; Arvola, René M.; Lou, Tzu Fang; Killingsworth, Jordan; Campbell, Zachary T.; Tanaka Hall, Traci M.; Goldstrohm, Aaron.

In: eLife, Vol. 5, No. AUGUST, e17096, 02.08.2016.

Research output: Contribution to journalArticle

Weidmann, CA, Qiu, C, Arvola, RM, Lou, TF, Killingsworth, J, Campbell, ZT, Tanaka Hall, TM & Goldstrohm, A 2016, 'Drosophila nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of pumilio', eLife, vol. 5, no. AUGUST, e17096. https://doi.org/10.7554/eLife.17096
Weidmann CA, Qiu C, Arvola RM, Lou TF, Killingsworth J, Campbell ZT et al. Drosophila nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of pumilio. eLife. 2016 Aug 2;5(AUGUST). e17096. https://doi.org/10.7554/eLife.17096
Weidmann, Chase A. ; Qiu, Chen ; Arvola, René M. ; Lou, Tzu Fang ; Killingsworth, Jordan ; Campbell, Zachary T. ; Tanaka Hall, Traci M. ; Goldstrohm, Aaron. / Drosophila nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of pumilio. In: eLife. 2016 ; Vol. 5, No. AUGUST.
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