Argonaute bypasses cellular obstacles without hindrance during target search

Tao Ju Cui; Misha Klein; Jorrit W. Hegge; Stanley D. Chandradoss; John van der Oost; Martin Depken; Chirlmin Joo

doi:10.1038/s41467-019-12415-y

Argonaute bypasses cellular obstacles without hindrance during target search

Tao Ju Cui, Misha Klein, Jorrit W. Hegge, Stanley D. Chandradoss, John van der Oost, Martin Depken^*, Chirlmin Joo

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

14 Citations (Scopus)

Abstract

Argonaute (Ago) proteins are key players in both gene regulation (eukaryotes) and host defense (prokaryotes). Acting on single-stranded nucleic-acid substrates, Ago relies on base pairing between a small nucleic-acid guide and its complementary target sequences for specificity. To efficiently scan nucleic-acid chains for targets, Ago diffuses laterally along the substrate and must bypass secondary structures as well as protein barriers. Using single-molecule FRET in conjunction with kinetic modelling, we reveal that target scanning is mediated through loose protein-nucleic acid interactions, allowing Ago to slide short distances over secondary structures, as well as to bypass protein barriers via intersegmental transfer. Our combined single-molecule experiment and kinetic modelling approach may serve as a platform to dissect search processes and study the effect of sequence on search kinetics for other nucleic acid-guided proteins.

Original language	English
Article number	4390
Journal	Nature Communications
Volume	10
DOIs	https://doi.org/10.1038/s41467-019-12415-y
Publication status	Published - 26 Sept 2019

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title = "Argonaute bypasses cellular obstacles without hindrance during target search",

abstract = "Argonaute (Ago) proteins are key players in both gene regulation (eukaryotes) and host defense (prokaryotes). Acting on single-stranded nucleic-acid substrates, Ago relies on base pairing between a small nucleic-acid guide and its complementary target sequences for specificity. To efficiently scan nucleic-acid chains for targets, Ago diffuses laterally along the substrate and must bypass secondary structures as well as protein barriers. Using single-molecule FRET in conjunction with kinetic modelling, we reveal that target scanning is mediated through loose protein-nucleic acid interactions, allowing Ago to slide short distances over secondary structures, as well as to bypass protein barriers via intersegmental transfer. Our combined single-molecule experiment and kinetic modelling approach may serve as a platform to dissect search processes and study the effect of sequence on search kinetics for other nucleic acid-guided proteins.",

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AU - Cui, Tao Ju

AU - Klein, Misha

AU - Hegge, Jorrit W.

AU - Chandradoss, Stanley D.

AU - van der Oost, John

AU - Depken, Martin

AU - Joo, Chirlmin

PY - 2019/9/26

Y1 - 2019/9/26

N2 - Argonaute (Ago) proteins are key players in both gene regulation (eukaryotes) and host defense (prokaryotes). Acting on single-stranded nucleic-acid substrates, Ago relies on base pairing between a small nucleic-acid guide and its complementary target sequences for specificity. To efficiently scan nucleic-acid chains for targets, Ago diffuses laterally along the substrate and must bypass secondary structures as well as protein barriers. Using single-molecule FRET in conjunction with kinetic modelling, we reveal that target scanning is mediated through loose protein-nucleic acid interactions, allowing Ago to slide short distances over secondary structures, as well as to bypass protein barriers via intersegmental transfer. Our combined single-molecule experiment and kinetic modelling approach may serve as a platform to dissect search processes and study the effect of sequence on search kinetics for other nucleic acid-guided proteins.

AB - Argonaute (Ago) proteins are key players in both gene regulation (eukaryotes) and host defense (prokaryotes). Acting on single-stranded nucleic-acid substrates, Ago relies on base pairing between a small nucleic-acid guide and its complementary target sequences for specificity. To efficiently scan nucleic-acid chains for targets, Ago diffuses laterally along the substrate and must bypass secondary structures as well as protein barriers. Using single-molecule FRET in conjunction with kinetic modelling, we reveal that target scanning is mediated through loose protein-nucleic acid interactions, allowing Ago to slide short distances over secondary structures, as well as to bypass protein barriers via intersegmental transfer. Our combined single-molecule experiment and kinetic modelling approach may serve as a platform to dissect search processes and study the effect of sequence on search kinetics for other nucleic acid-guided proteins.

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DO - 10.1038/s41467-019-12415-y

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Argonaute bypasses cellular obstacles without hindrance during target search

Abstract

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