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Abstract RNA‐protein interactions play essential roles in regulating gene expression. While some RNA‐protein interactions are “specific”, that is, the RNA‐binding proteins preferentially bind to particular RNA sequence or structural motifs, others are “non‐RNA specific.” Deciphering the protein‐RNA recognition code is essential for comprehending the functional implications of these interactions and for developing new therapies for many diseases. Because of the high cost of experimental determination of protein‐RNA interfaces, there is a need for computational methods to identify RNA‐binding residues in proteins. While most of the existing computational methods for predicting RNA‐binding residues in RNA‐binding proteins are oblivious to the characteristics of the partner RNA, there is growing interest in methods for partner‐specific prediction of RNA binding sites in proteins. In this work, we assess the performance of two recently published partner‐specific protein‐RNA interface prediction tools, PS‐PRIP, and PRIdictor, along with our own new tools. Specifically, we introduce a novel metric, RNA‐specificity metric (RSM), for quantifying the RNA‐specificity of the RNA binding residues predicted by such tools. Our results show that the RNA‐binding residues predicted by previously published methods are oblivious to the characteristics of the putative RNA binding partner. Moreover, when evaluated using partner‐agnostic metrics, RNA partner‐specific methods are outperformed by the state‐of‐the‐art partner‐agnostic methods. We conjecture that either (a) the protein‐RNA complexes in PDB are not representative of the protein‐RNA interactions in nature, or (b) the current methods for partner‐specific prediction of RNA‐binding residues in proteins fail to account for the differences in RNA partner‐specific versus partner‐agnostic protein‐RNA interactions, or both.
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This content will become publicly available on May 12, 2026
Long non-coding RNA hsr-omega provides scaffolding for the nuclear domain B-body
Nuclear domains (NDs)—such as nucleoli or nuclear speckles—are membraneless, organelle-like compartments that concentrate and retain nuclear proteins. Despite their ubiquitous presence in the cell, the organization, regulation, and functions of many NDs remain poorly understood. The B-body is a prominent nuclear domain observed in developing flight muscles of Drosophila. In this study, we expand the understanding of B-body composition and function. We identify several additional RNA-binding proteins (RBPs) as B-body components and show that some proteins can dynamically disappear from this ND. We further demonstrate that the B-body contains an RNA component, which was identified as the long non-coding RNA hsrω. Genetic analyses reveal that hsrω acts as a structural scaffold for the B-body, and its depletion leads to B-body disassembly. In contrast, loss of the resident protein Bruno (Bru), a splicing factor, does not compromise B-body integrity. Finally, we show that imbalance in the hsrω/Bru ratio promotes Bru aggregation, suggesting that the B-body plays a role in maintaining nuclear protein homeostasis.
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- Award ID(s):
- 2042814
- PAR ID:
- 10595667
- Publisher / Repository:
- BIORXIV
- Date Published:
- Journal Name:
- bioRxiv
- ISSN:
- 2692-8205
- Subject(s) / Keyword(s):
- lncRNA nucleus nuclear domains B-body nuclear architecture Drosophila
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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