Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis

RNA-targeting small molecules, particularly RIBOnuclease TArgeting Chimeras (RIBOTACs), represent a powerful and promising therapeutic approach by selectively degrading RNAs through ribonuclease (RNase) recruitment. Despite their potential, the development of effective RNase recruitment tools is sti...

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Main Authors: Elias Khaskia, Raphael I. Benhamou
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024173264
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author Elias Khaskia
Raphael I. Benhamou
author_facet Elias Khaskia
Raphael I. Benhamou
author_sort Elias Khaskia
collection DOAJ
description RNA-targeting small molecules, particularly RIBOnuclease TArgeting Chimeras (RIBOTACs), represent a powerful and promising therapeutic approach by selectively degrading RNAs through ribonuclease (RNase) recruitment. Despite their potential, the development of effective RNase recruitment tools is still in its early stages and remains a critical area of research. Ribonuclease L (RNase L) is a key ribonuclease targeted by RIBOTACs, yet the tools available for studying RNase L are limited. In this study, we introduce novel fluorescent ribonuclease binders that enhance the visualization and investigation of RNase L activity. Our findings provide new insights into RNase L dynamics and RNA degradation pathways, paving the way for more effective RNA-targeted degradation strategies. Furthermore, we explore the versatility of these conjugates for real-time tracking of RNase L localization, intracellular trafficking, and mechanistic studies. These fluorescent probes also enable high-throughput fluorescence-based assays to identify small molecules that bind and recruit RNase L, advancing RNA-targeted therapeutic approaches.
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institution Kabale University
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publishDate 2025-01-01
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spelling doaj-art-3624d5b1d73c4f7eb30a4c40411902fa2025-01-17T04:50:49ZengElsevierHeliyon2405-84402025-01-01111e41295Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysisElias Khaskia0Raphael I. Benhamou1The Institute for Drug Research of the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelCorresponding author.; The Institute for Drug Research of the School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelRNA-targeting small molecules, particularly RIBOnuclease TArgeting Chimeras (RIBOTACs), represent a powerful and promising therapeutic approach by selectively degrading RNAs through ribonuclease (RNase) recruitment. Despite their potential, the development of effective RNase recruitment tools is still in its early stages and remains a critical area of research. Ribonuclease L (RNase L) is a key ribonuclease targeted by RIBOTACs, yet the tools available for studying RNase L are limited. In this study, we introduce novel fluorescent ribonuclease binders that enhance the visualization and investigation of RNase L activity. Our findings provide new insights into RNase L dynamics and RNA degradation pathways, paving the way for more effective RNA-targeted degradation strategies. Furthermore, we explore the versatility of these conjugates for real-time tracking of RNase L localization, intracellular trafficking, and mechanistic studies. These fluorescent probes also enable high-throughput fluorescence-based assays to identify small molecules that bind and recruit RNase L, advancing RNA-targeted therapeutic approaches.http://www.sciencedirect.com/science/article/pii/S2405844024173264RIBOTACRNase LFluorescent probesSubcellular localization
spellingShingle Elias Khaskia
Raphael I. Benhamou
Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis
Heliyon
RIBOTAC
RNase L
Fluorescent probes
Subcellular localization
title Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis
title_full Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis
title_fullStr Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis
title_full_unstemmed Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis
title_short Leveraging RIBOTAC technology: Fluorescent RNase L probes for live-cell imaging and function analysis
title_sort leveraging ribotac technology fluorescent rnase l probes for live cell imaging and function analysis
topic RIBOTAC
RNase L
Fluorescent probes
Subcellular localization
url http://www.sciencedirect.com/science/article/pii/S2405844024173264
work_keys_str_mv AT eliaskhaskia leveragingribotactechnologyfluorescentrnaselprobesforlivecellimagingandfunctionanalysis
AT raphaelibenhamou leveragingribotactechnologyfluorescentrnaselprobesforlivecellimagingandfunctionanalysis