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Highly structured RNA molecules usually interact with each other, and associate with various RNA-binding proteins, to regulate critical biological processes. However, RNA structures and interactions in intact cells remain largely unknown. Here, by coupling proximity ligation mediated by RNA-binding proteins with deep sequencing, we report an RNA in situ conformation sequencing (RIC-seq) technology for the global profiling of intra- and intermolecular RNA-RNA interactions. This technique not only recapitulates known RNA secondary structures and tertiary interactions, but also facilitates the generation of three-dimensional (3D) interaction maps of RNA in human cells. Using these maps, we identify noncoding RNA targets globally, and discern RNA topological domains and trans-interacting hubs. We reveal that the functional connectivity of enhancers and promoters can be assigned using their pairwise-interacting RNAs. Furthermore, we show that CCAT1-5L--a super-enhancer hub RNA--interacts with the RNA-binding protein hnRNPK, as well as RNA derived from the MYC promoter and enhancer, to boost MYC transcription by modulating chromatin looping. Our study demonstrates the power and applicability of RIC-seq in discovering the 3D structures, interactions and regulatory roles of RNA. RNA in situ conformation sequencing (RIC-seq) enables the generation of three-dimensional interaction maps of RNA in cells, which sheds light on the interactions and regulatory functions of RNA., Author(s): Zhaokui Cai [sup.1] [sup.2] , Changchang Cao [sup.1] , Lei Ji [sup.1] , Rong Ye [sup.1] [sup.2] , Di Wang [sup.1] [sup.2] , Cong Xia [sup.3] , Sui Wang [...]

H2S is an endogenous gas signaling molecule and its multiple biological effects have been demonstrated. The abnormal level of H2S is closely related to the occurrence and development of many diseases, and H2S donors has important pharmacological implications. In recent years, H2S donors represented by ADTOH (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) are often used to synthesize new 'conjugate' compounds that can release H2S and parent drugs. These hybrids retain the pharmacological activity of the parent drugs and H2S and have a synergistic effect. ADTOH and parent drug hybrids have become one of the important strategies for the development of H2S donor conjugate drugs. This review summarizes molecular hybrids between ADTOH and clinical drugs to provide new ideas for the study of H2S donor drug design. [ABSTRACT FROM AUTHOR]

Postnatal cardiac development requires the orchestrated maturation of diverse cellular components for which unifying control mechanisms are still lacking. Using full-length sequencing, we examined the transcriptomic landscape of the maturating mouse heart (E18.5-P28) at single-cell and transcript isoform resolution. We identified dynamically changing intercellular networks as a molecular basis of the maturing heart and alternative splicing (AS) as a common mechanism that distinguished developmental age. Manipulation of RNA-binding proteins (RBPs) remodeled the AS landscape, cardiac cell maturation, and intercellular communication through direct binding of splice targets, which were enriched for functions related to general, as well as cell-type-specific, maturation. Overexpression of an RBP nuclear cap-binding protein subunit 2 (NCBP2) in neonatal hearts repressed cardiac maturation. Together, our data suggest AS regulation by RBPs as an organ-level control mechanism in mammalian postnatal cardiac development and provide insight into the possibility of manipulating RBPs for therapeutic purposes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

H 2 S is an endogenous gas signaling molecule and its multiple biological effects have been demonstrated. The abnormal level of H 2 S is closely related to the occurrence and development of many diseases, and H 2 S donors has important pharmacological implications. In recent years, H 2 S donors represented by ADTOH (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) are often used to synthesize new 'conjugate' compounds that can release H 2 S and parent drugs. These hybrids retain the pharmacological activity of the parent drugs and H 2 S and have a synergistic effect. ADTOH and parent drug hybrids have become one of the important strategies for the development of H 2 S donor conjugate drugs. This review summarizes molecular hybrids between ADTOH and clinical drugs to provide new ideas for the study of H 2 S donor drug design.