dorsal/arxiv
View SchemaEncoding folding paths of RNA switches
| Authors | A. Xayaphoummine, V. Viasnoff, S. Harlepp, H. Isambert |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0611071 |
| URL | https://arxiv.org/abs/q-bio/0611071 |
Abstract
RNA co-transcriptional folding has long been suspected to play an active role in helping proper native folding of ribozymes and structured regulatory motifs in mRNA untranslated regions. Yet, the underlying mechanisms and coding requirements for efficient co-transcriptional folding remain unclear. Traditional approaches have intrinsic limitations to dissect RNA folding paths, as they rely on sequence mutations or circular permutations that typically perturb both RNA folding paths and equilibrium structures. Here, we show that exploiting sequence symmetries instead of mutations can circumvent this problem by essentially decoupling folding paths from equilibrium structures of designed RNA sequences. Using bistable RNA switches with symmetrical helices conserved under sequence reversal, we demonstrate experimentally that native and transiently formed helices can guide efficient co-transcriptional folding into either long-lived structure of these RNA switches. Their folding path is controlled by the order of helix nucleations and subsequent exchanges during transcription, and may also be redirected by transient antisense interactions. Hence, transient intra- and intermolecular base pair interactions can effectively regulate the folding of nascent RNA molecules into different native structures, provided limited coding requirements, as discussed from an information theory perspective. This constitutive coupling between RNA synthesis and RNA folding regulation may have enabled the early emergence of autonomous RNA-based regulation networks.
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"abstract": "RNA co-transcriptional folding has long been suspected to play an active role\nin helping proper native folding of ribozymes and structured regulatory motifs\nin mRNA untranslated regions. Yet, the underlying mechanisms and coding\nrequirements for efficient co-transcriptional folding remain unclear.\nTraditional approaches have intrinsic limitations to dissect RNA folding paths,\nas they rely on sequence mutations or circular permutations that typically\nperturb both RNA folding paths and equilibrium structures. Here, we show that\nexploiting sequence symmetries instead of mutations can circumvent this problem\nby essentially decoupling folding paths from equilibrium structures of designed\nRNA sequences. Using bistable RNA switches with symmetrical helices conserved\nunder sequence reversal, we demonstrate experimentally that native and\ntransiently formed helices can guide efficient co-transcriptional folding into\neither long-lived structure of these RNA switches. Their folding path is\ncontrolled by the order of helix nucleations and subsequent exchanges during\ntranscription, and may also be redirected by transient antisense interactions.\nHence, transient intra- and intermolecular base pair interactions can\neffectively regulate the folding of nascent RNA molecules into different native\nstructures, provided limited coding requirements, as discussed from an\ninformation theory perspective. This constitutive coupling between RNA\nsynthesis and RNA folding regulation may have enabled the early emergence of\nautonomous RNA-based regulation networks.",
"arxiv_id": "q-bio/0611071",
"authors": [
"A. Xayaphoummine",
"V. Viasnoff",
"S. Harlepp",
"H. Isambert"
],
"categories": [
"q-bio.BM",
"q-bio.MN"
],
"title": "Encoding folding paths of RNA switches",
"url": "https://arxiv.org/abs/q-bio/0611071"
},
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