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🧵 (7/7) Combining different methodologies (smFRET, NMR & reporter gene assays) we developed a framework that can now be used to study similar processes in other biological systems! 🧬 hashtag#single-molecule hashtag#FRET hashtag#RNA hashtag#translation hashtag#Biophysics

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🧵 (6/7) Why this matters: Understanding these molecular mechanisms helps us grasp how cells regulate their genes through different complex assembly mechanisms.

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🧵 (5/7) These mechanisms work together to achieve tight translation repression. And it’s the first time seeing this complex assembly in real-time!

🧵 (4/7) Key Finding #4: A third protein (Hrp48) acts as a molecular "doorstop" - preventing RNA from displacing Sxl and Unr. 🚪

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🧵 (3/7) Key Finding #3: RNA-bound Sxl helps recruit another protein (Unr) 500x faster! Like a molecular speedway for protein assembly. 🏃‍♂️💨

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🧵 (2/7) Key Finding #2: We saw Sxl can slide along RNA between binding sites instead of just binding and falling off. This helps it stay attached longer. 🏄‍♂️

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🧵 (1/7) Key Finding #1: We discovered Sex-lethal (Sxl) alone, despite its high affinity, transiently samples its target sites

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In a collaboration between the @hennig-lab.bsky.social and @olivierduss.bsky.social labs we revealed how proteins work together to control gene expression through mRNA translation repression! Using single-molecule microscopy, we watched individual molecules in action. doi.org/10.1101/2025... 🧵

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🧵 (7/7) Combining different methodologies (smFRET, NMR & reporter gene assays) we developed a framework that can now be used to study similar processes in other biological systems! 🧬 #single-molecule #FRET #RNA #translation #Biophysics

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🧵 (6/7) Why this matters: Understanding these molecular mechanisms helps us grasp how cells regulate their genes through different complex assembly mechanisms.

100

🧵 (5/7) These mechanisms work together to achieve tight translation repression. And it’s the first time seeing this complex assembly in real-time!

100

🧵 (4/7) Key Finding #4: A third protein (Hrp48) acts as a molecular "doorstop" - preventing RNA from displacing Sxl and Unr. 🚪

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🧵 (3/7) Key Finding #3: RNA-bound Sxl helps recruit another protein (Unr) 500x faster! Like a molecular speedway for protein assembly. 🏃‍♂️💨

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🧵 (2/7) Key Finding #2: We saw Sxl can slide along RNA between binding sites instead of just binding and falling off. This helps it stay attached longer. 🏄‍♂️

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Laura Rustarazo-Calvo @laura-rustarazo.bsky.social · 27/03/2025

🧵 (1/7) Key Finding #1: We discovered Sex-lethal (Sxl) alone, despite its high affinity, transiently samples its target sites

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Reposted by Marco Payr

🎉 Excited to share our new work: “Adhesion-driven tissue rigidification triggers epithelial cell polarity”, now on @biorxivpreprint.bsky.social ! A huge thank you to @nicolettapetridou.bsky.social, Bernat, @crisp-c.bsky.social, Adrián, and everyone involved! 🙌 🧵⤵️

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Reposted by Marco Payr

Christophe 🔬 Leterrier @christlet.bsky.social · 16/01/2025

There are new stable red fluorescent proteins coming, but organic fluorophores are fighting back! Impressive photostability of Phoenix Fluor 555 for live-cell imaging with HaloTag, just out in @naturemethods.bsky.social: doi.org/10.1038/s415...

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✴️ Single-molecule approaches bridge the gap between structural snapshots & real-world dynamics. As an example, smFRET can track dynamics of protein·RNA complex assembly and how it is coupled to RNA restructuring.

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🧪 How can we study this? Have a closer look at single-molecule fluorescence microscopy! Focusing on translation repression mechanisms, the method can reveal: - Real-time assembly of complexes - Rare intermediate states - Kinetics of translation repression/activation with spatial context

- Recruitment-blocking of the 43S PIC by 3’ UTR-bound proteins like Sex-lethal in Drosophila. 🧬 - microRNA-induced silencing complexes (miRISCs) - eIF4E-binding proteins (4E-BPs) masking initiation factors

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🎯 Spotlight on the 3’ UTR! This region binds regulatory factors that can interfere with the 43S pre-initiation complex (PIC)—a key player during translation initiation. But how do RNA-binding proteins interfere with initiation? 🤔 Mechanisms of action can be:

🔑 A key focus is translation repression: halting protein synthesis when & where needed. We explore different mechanisms that contribute to translation repression such as: - RNA-binding proteins - microRNAs - RNA dynamics

🚦Translation repression isn’t just academic—its understanding is vital for diseases like cancer, neurodevelopmental disorders, and viral infections. Understanding these dynamics opens doors for targeted therapies.

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📖 Our review (doi.org/10.1042/BST2...) highlights how dynamic techniques like smFRET and in vivo single-molecule imaging gives us the tools to better understand translational control and the mechanisms at action. A step closer to precision medicine! 🩺

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