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Using mice lacking ADAR2 alone or combined with catalytically inactive ADAR1, the work connects ADAR perturbations to shifts in alternative splicing and accompanying changes in other RNA modifications, while identifying candidate circular RNA profiles and potential inosine sites within circular RNAs.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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is the main focus of the study on mouse brain RNA biology?","Question",{"text":63,"@type":64},"The study focuses on how RNA modifications relate to alternative splicing and circular RNA formation in the mouse brain, with special attention to inosine and ADAR enzymes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were inosine-related effects assessed in vivo?",{"text":68,"@type":64},"The researchers used mice lacking ADAR2 alone or in combination with catalytically inactive ADAR1, then evaluated changes in alternative splicing and associated RNA modification levels.",{"name":70,"@type":61,"acceptedAnswer":71},"What additional circular RNA findings were reported?",{"text":72,"@type":64},"The study identified novel candidate circular RNA profiles in wildtype and mutant mice and detected potential inosine sites within circular RNAs.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},450450,1791180846,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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and circular RNA landscape in the mouse brain: inosine and beyond  \nErika Larrea1,2,3,4, MaitenaTellaetxe-Abete5, Yan Peng2,3,4,6, Yujie Zhang2,3,4, Shuangshuang Feng2,3,4,7, Kaidong Lu2,3,4,8, Liang Xue2,3,4, Taisuke Nakahama9,10, Yukio Kawahara9,10 & Magdalena J. Koziol2,3,4􀀍  \nRNA modifications in the brain can be essential for regulating the transcriptome and brain function. Our study unveils the landscape of different RNA modifications associated with splicing within the mouse brain. Focusing on inosine, known for its role in alternative splicing modulation and enriched in introns, we investigated its influence using mice lacking ADAR2 alone or in combination with catalytically inactive ADAR1. While some alternative splicing-regulatory roles of inosine andADAR enzymes are established, we observe that altering ADAR2 andADAR1/ADAR2 is associated with changes in alternative splicing and coincides with shifts in levels of other RNA modification. Through the utilization of an innovative approach, we identified novel candidate circular RNA profiles in wildtype and mutant mice and detected potential inosine sites within circular RNAs. Collectively, our findings underscore a complex interplay among RNA modifications, alternative splicing, circular RNAsin the mouse brain.  \nRNA modifications, regulated by specialized enzymes, expand the diversity of the transcriptome and are crucial for maintaining cellular and organ homeostasis1. In the brain, RNA modifications seem particularly abundant and are essential for brain development, neuronal differentiation, and synapse formation2. Given their importance in key physiological functions, it is not surprising that dysregulation of RNA modifications or the enzymes that mediate these modifications can cause neurological and neurodegenerative disorders3–6 and be associated with aging7. Consequently, delving into the realm of RNA modifications in the brain emerges as a critical avenue of research.  \nRNA modifications can alter which proteins bind to RNA, either directly or indirectly, by modifying RNA secondary structures8. As such, RNA modifications can affect multiple processes, including transcription, nuclear export and stabilization9–12. Furthermore, internal mRNA modifications can potentially promote changes in the recognition of splicing factors or the assembly of the spliceosome, impacting splice site recognition and therefore altering canonical RNA splicing as well as backsplicing. Backsplicing, a mechanism responsible for generating circular RNAs (circRNAs) by joining splice sites in reverse order, adds another layer of complexity to RNA regulation13. Factors that bring backsplice sites into proximity by changing RNA structure promote circRNA production14. Given that any RNA modifications may influence RNA secondary structure15, they are also likely regulators ofcircRNA formation. circRNAs have diverse functions in cells, including acting as miRNA sponges, regulating transcription, interacting with proteins, potentially being translated into proteins, serving as scaffolds for molecular complexes, and influencing alternative splicing (AS)16. AS variants exhibit remarkable diversity, while circRNAs are notably abundant in the brain. Both play pivotal roles in synaptic plasticity and aging-related  \n1Tsinghua University, Beijing 100084, China. 2Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China. 3Chinese Institute for Brain Research, Beijing, Beijing 102206, China. 4Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing 102206, China. 5Intelligent Systems Group, Computer Science Faculty, University of the Basque Country, 20018 Donostia/San Sebastian, Spain. 6Peking University, Beijing 100871, China. 7State Key Laboratory of Cognitive Neuroscience and Learning, Be","cbCainUnG5QOX6tu","https://ap.wps.com/l/cbCainUnG5QOX6tu","pdf",3103936,23,"English","# Background and significance\n## RNA modifications in brain function and disease\n## Links between RNA modifications, splicing, and circular RNA biogenesis\n# Study aim and strategy\n## Enrichment in intron-containing regions\n## Screening RNA modification candidates\n# Experimental design and results\n## RNA modification enrichment in nuclear polyA RNA and splicing-inhibited mRNAs","[{\"question\":\"What is the main focus of the study on mouse brain RNA biology?\",\"answer\":\"The study focuses on how RNA modifications relate to alternative splicing and circular RNA formation in the mouse brain, with special attention to inosine and ADAR enzymes.\"},{\"question\":\"How were inosine-related effects assessed in vivo?\",\"answer\":\"The researchers used mice lacking ADAR2 alone or in combination with catalytically inactive ADAR1, then evaluated changes in alternative splicing and associated RNA modification levels.\"},{\"question\":\"What additional circular RNA findings were reported?\",\"answer\":\"The study identified novel candidate circular RNA profiles in wildtype and mutant mice and detected potential inosine sites within circular RNAs.\"}]","RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond | PDF",1790733228,58]