{"title":"通过设计具有核壳结构域的 Arc 蛋白来增强 mRNA 的相互作用","authors":"Vaibhav Upadhayay, Wenchao Gu, Qiuming Yu","doi":"10.1021/acs.langmuir.4c03151","DOIUrl":null,"url":null,"abstract":"Activity-regulated cytoskeleton-associated protein (Arc) forms virus-like capsids for mRNA transport between neurons. Unlike HIV-1 Group-specific Antigen (Gag), which uses its Nucleocapsid (NC) domain to bind HIV-1 genomic mRNA, mammalian Arc lacks the NC domain, and their direct mRNA binding interactions remain underexplored. This study examined rat Arc’s binding to rat Arc 5′ UTR (A5U), HIV-1 5′ UTR (H5U), and GFP mRNAs, revealing weak binding with no significant preference. Adding the HIV-1 NC domain to rArc’s C-terminus significantly improved binding to H5U, while also showing substantial binding to A5U at about 60% of its H5U level and exhibiting twice the affinity for A5U over GFP mRNA. Importantly, rArc-NC binds 3.4 times more A5U and H5U than GST-NC, indicating that rArc NTD-CA aids mRNA binding by HIV-1 NC. These findings suggest a conserved Gag protein–mRNA interaction mechanism, highlighting the potential for developing mRNA delivery systems that combine endogenous Gag NTD-CA with retroviral NC and UTRs.","PeriodicalId":50,"journal":{"name":"Langmuir","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhancing mRNA Interactions by Engineering the Arc Protein with Nucleocapsid Domain\",\"authors\":\"Vaibhav Upadhayay, Wenchao Gu, Qiuming Yu\",\"doi\":\"10.1021/acs.langmuir.4c03151\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Activity-regulated cytoskeleton-associated protein (Arc) forms virus-like capsids for mRNA transport between neurons. Unlike HIV-1 Group-specific Antigen (Gag), which uses its Nucleocapsid (NC) domain to bind HIV-1 genomic mRNA, mammalian Arc lacks the NC domain, and their direct mRNA binding interactions remain underexplored. This study examined rat Arc’s binding to rat Arc 5′ UTR (A5U), HIV-1 5′ UTR (H5U), and GFP mRNAs, revealing weak binding with no significant preference. Adding the HIV-1 NC domain to rArc’s C-terminus significantly improved binding to H5U, while also showing substantial binding to A5U at about 60% of its H5U level and exhibiting twice the affinity for A5U over GFP mRNA. Importantly, rArc-NC binds 3.4 times more A5U and H5U than GST-NC, indicating that rArc NTD-CA aids mRNA binding by HIV-1 NC. These findings suggest a conserved Gag protein–mRNA interaction mechanism, highlighting the potential for developing mRNA delivery systems that combine endogenous Gag NTD-CA with retroviral NC and UTRs.\",\"PeriodicalId\":50,\"journal\":{\"name\":\"Langmuir\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Langmuir\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.langmuir.4c03151\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Langmuir","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.langmuir.4c03151","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Enhancing mRNA Interactions by Engineering the Arc Protein with Nucleocapsid Domain
Activity-regulated cytoskeleton-associated protein (Arc) forms virus-like capsids for mRNA transport between neurons. Unlike HIV-1 Group-specific Antigen (Gag), which uses its Nucleocapsid (NC) domain to bind HIV-1 genomic mRNA, mammalian Arc lacks the NC domain, and their direct mRNA binding interactions remain underexplored. This study examined rat Arc’s binding to rat Arc 5′ UTR (A5U), HIV-1 5′ UTR (H5U), and GFP mRNAs, revealing weak binding with no significant preference. Adding the HIV-1 NC domain to rArc’s C-terminus significantly improved binding to H5U, while also showing substantial binding to A5U at about 60% of its H5U level and exhibiting twice the affinity for A5U over GFP mRNA. Importantly, rArc-NC binds 3.4 times more A5U and H5U than GST-NC, indicating that rArc NTD-CA aids mRNA binding by HIV-1 NC. These findings suggest a conserved Gag protein–mRNA interaction mechanism, highlighting the potential for developing mRNA delivery systems that combine endogenous Gag NTD-CA with retroviral NC and UTRs.
期刊介绍:
Langmuir is an interdisciplinary journal publishing articles in the following subject categories:
Colloids: surfactants and self-assembly, dispersions, emulsions, foams
Interfaces: adsorption, reactions, films, forces
Biological Interfaces: biocolloids, biomolecular and biomimetic materials
Materials: nano- and mesostructured materials, polymers, gels, liquid crystals
Electrochemistry: interfacial charge transfer, charge transport, electrocatalysis, electrokinetic phenomena, bioelectrochemistry
Devices and Applications: sensors, fluidics, patterning, catalysis, photonic crystals
However, when high-impact, original work is submitted that does not fit within the above categories, decisions to accept or decline such papers will be based on one criteria: What Would Irving Do?
Langmuir ranks #2 in citations out of 136 journals in the category of Physical Chemistry with 113,157 total citations. The journal received an Impact Factor of 4.384*.
This journal is also indexed in the categories of Materials Science (ranked #1) and Multidisciplinary Chemistry (ranked #5).