Daniel Gussakovsky, Mira J F Brown, Higor Sette Pereira, Markus Meier, G Pauline Padilla-Meier, Nicole A Black, Evan P Booy, Jörg Stetefeld, Trushar R Patel, Sean A McKenna
{"title":"Alu RNA假结改变影响SRP9/SRP14的关联。","authors":"Daniel Gussakovsky, Mira J F Brown, Higor Sette Pereira, Markus Meier, G Pauline Padilla-Meier, Nicole A Black, Evan P Booy, Jörg Stetefeld, Trushar R Patel, Sean A McKenna","doi":"10.1261/rna.080359.124","DOIUrl":null,"url":null,"abstract":"<p><p>There are over 1 million Alu elements in the human genome which can be transcribed into discrete, RNA polymerase III transcribed noncoding Alu RNAs. These Alu RNAs often interact with and are regulated by the protein heterodimer SRP9/SRP14. This interaction is dependent on a 5' pseudoknot domain in the Alu RNA that is thought to be held together by a canonical nucleotide triad within a U-turn motif. Herein, we discover a significant reduction in BC200 expression after mutation of a critical guanosine in the U-turn motif within its pseudoknot domain. We studied a recently discovered short human Alu RNA, EB120, which lacks the canonical Alu RNA U-turn nucleotide triad. We tested the expression of EB120 in 18 different human cell lines and tissues. EB120 was found to lack association with SRP9/SRP14 in a cellular context. Small-angle X-ray scattering followed by atomistic computation structure prediction suggests the BC200 Alu domain and its U-turn mutant both possess a canonical Alu RNA fold, while EB120 lacks one. Our results highlight the structural diversity of Alu RNA, and the impact mutations may have on Alu RNA function.</p>","PeriodicalId":21401,"journal":{"name":"RNA","volume":" ","pages":"1154-1175"},"PeriodicalIF":4.2000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265939/pdf/","citationCount":"0","resultStr":"{\"title\":\"Alu RNA pseudoknot alterations influence SRP9/SRP14 association.\",\"authors\":\"Daniel Gussakovsky, Mira J F Brown, Higor Sette Pereira, Markus Meier, G Pauline Padilla-Meier, Nicole A Black, Evan P Booy, Jörg Stetefeld, Trushar R Patel, Sean A McKenna\",\"doi\":\"10.1261/rna.080359.124\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>There are over 1 million Alu elements in the human genome which can be transcribed into discrete, RNA polymerase III transcribed noncoding Alu RNAs. These Alu RNAs often interact with and are regulated by the protein heterodimer SRP9/SRP14. This interaction is dependent on a 5' pseudoknot domain in the Alu RNA that is thought to be held together by a canonical nucleotide triad within a U-turn motif. Herein, we discover a significant reduction in BC200 expression after mutation of a critical guanosine in the U-turn motif within its pseudoknot domain. We studied a recently discovered short human Alu RNA, EB120, which lacks the canonical Alu RNA U-turn nucleotide triad. We tested the expression of EB120 in 18 different human cell lines and tissues. EB120 was found to lack association with SRP9/SRP14 in a cellular context. Small-angle X-ray scattering followed by atomistic computation structure prediction suggests the BC200 Alu domain and its U-turn mutant both possess a canonical Alu RNA fold, while EB120 lacks one. Our results highlight the structural diversity of Alu RNA, and the impact mutations may have on Alu RNA function.</p>\",\"PeriodicalId\":21401,\"journal\":{\"name\":\"RNA\",\"volume\":\" \",\"pages\":\"1154-1175\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265939/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RNA\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1261/rna.080359.124\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RNA","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1261/rna.080359.124","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Alu RNA pseudoknot alterations influence SRP9/SRP14 association.
There are over 1 million Alu elements in the human genome which can be transcribed into discrete, RNA polymerase III transcribed noncoding Alu RNAs. These Alu RNAs often interact with and are regulated by the protein heterodimer SRP9/SRP14. This interaction is dependent on a 5' pseudoknot domain in the Alu RNA that is thought to be held together by a canonical nucleotide triad within a U-turn motif. Herein, we discover a significant reduction in BC200 expression after mutation of a critical guanosine in the U-turn motif within its pseudoknot domain. We studied a recently discovered short human Alu RNA, EB120, which lacks the canonical Alu RNA U-turn nucleotide triad. We tested the expression of EB120 in 18 different human cell lines and tissues. EB120 was found to lack association with SRP9/SRP14 in a cellular context. Small-angle X-ray scattering followed by atomistic computation structure prediction suggests the BC200 Alu domain and its U-turn mutant both possess a canonical Alu RNA fold, while EB120 lacks one. Our results highlight the structural diversity of Alu RNA, and the impact mutations may have on Alu RNA function.
期刊介绍:
RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.