{"title":"Context-dependent structure formation of hairpin motifs in bacteriophage MS2 genomic RNA.","authors":"Veronika Bukina, Anže Božič","doi":"10.1016/j.bpj.2024.08.004","DOIUrl":null,"url":null,"abstract":"<p><p>Many functions of ribonucleic acid (RNA) rely on its ability to assume specific sequence-structure motifs. Packaging signals found in certain RNA viruses are one such prominent example of functional RNA motifs. These signals are short hairpin loops that interact with coat proteins and drive viral self-assembly. As they are found in different positions along the much longer genomic RNA, the formation of their correct structure occurs as a part of a larger context. Any changes to this context can consequently lead to changes in the structure of the motifs themselves. In fact, previous studies have shown that structure and function of RNA motifs can be highly context sensitive to the flanking sequence surrounding them. However, in what ways different flanking sequences influence the structure of an RNA motif they surround has yet to be studied in detail. We focus on a hairpin-rich region of the RNA genome of bacteriophage MS2-a well-studied RNA virus with a wide potential for use in biotechnology-and systematically examine context-dependent structural stability of 14 previously identified hairpin motifs, which include putative and confirmed packaging signals. Combining secondary and tertiary RNA structure prediction of the hairpin motifs placed in different contexts, ranging from the native genomic sequence to random RNA sequences and unstructured poly-U sequences, we determine different measures of motif structural stability. In this way, we show that while some motif structures can be stable in any context, others require specific context provided by the genome. Our results demonstrate the importance of context in RNA structure formation and how changes in the flanking sequence of an RNA motif sometimes lead to drastic changes in its structure. Structural stability of a motif in different contexts could provide additional insights into its functionality as well as assist in determining whether it remains functional when intentionally placed in other contexts.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480767/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysical journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.bpj.2024.08.004","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOPHYSICS","Score":null,"Total":0}
引用次数: 0
Abstract
Many functions of ribonucleic acid (RNA) rely on its ability to assume specific sequence-structure motifs. Packaging signals found in certain RNA viruses are one such prominent example of functional RNA motifs. These signals are short hairpin loops that interact with coat proteins and drive viral self-assembly. As they are found in different positions along the much longer genomic RNA, the formation of their correct structure occurs as a part of a larger context. Any changes to this context can consequently lead to changes in the structure of the motifs themselves. In fact, previous studies have shown that structure and function of RNA motifs can be highly context sensitive to the flanking sequence surrounding them. However, in what ways different flanking sequences influence the structure of an RNA motif they surround has yet to be studied in detail. We focus on a hairpin-rich region of the RNA genome of bacteriophage MS2-a well-studied RNA virus with a wide potential for use in biotechnology-and systematically examine context-dependent structural stability of 14 previously identified hairpin motifs, which include putative and confirmed packaging signals. Combining secondary and tertiary RNA structure prediction of the hairpin motifs placed in different contexts, ranging from the native genomic sequence to random RNA sequences and unstructured poly-U sequences, we determine different measures of motif structural stability. In this way, we show that while some motif structures can be stable in any context, others require specific context provided by the genome. Our results demonstrate the importance of context in RNA structure formation and how changes in the flanking sequence of an RNA motif sometimes lead to drastic changes in its structure. Structural stability of a motif in different contexts could provide additional insights into its functionality as well as assist in determining whether it remains functional when intentionally placed in other contexts.
期刊介绍:
BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.