Molecular crowding and RNA catalysis

2020 ◽  
Vol 18 (39) ◽  
pp. 7724-7739
Author(s):  
Saurja DasGupta
Keyword(s):  
Rna Folding ◽  
Rna Catalysis ◽  
Molecular Crowding

Molecular crowding promotes RNA folding and catalysis and could have played vital roles in the evolution of primordial ribozymes and protocells.

scholarly journals Ribozyme-catalysed RNA synthesis using triplet building blocks

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
James Attwater ◽  
Aditya Raguram ◽  
Alexey S Morgunov ◽  
Edoardo Gianni ◽  
Philipp Holliger
Keyword(s):  
Rna Synthesis ◽  
Rna Folding ◽  
Rna Replication ◽  
Building Blocks ◽  
Secondary Structures ◽  
Catalytic Subunit ◽  
Rna Catalysis ◽  
Apparent Paradox ◽  
In Vitro Evolution

RNA-catalyzed RNA replication is widely believed to have supported a primordial biology. However, RNA catalysis is dependent upon RNA folding, and this yields structures that can block replication of such RNAs. To address this apparent paradox, we have re-examined the building blocks used for RNA replication. We report RNA-catalysed RNA synthesis on structured templates when using trinucleotide triphosphates (triplets) as substrates, catalysed by a general and accurate triplet polymerase ribozyme that emerged from in vitro evolution as a mutualistic RNA heterodimer. The triplets cooperatively invaded and unraveled even highly stable RNA secondary structures, and support non-canonical primer-free and bidirectional modes of RNA synthesis and replication. Triplet substrates thus resolve a central incongruity of RNA replication, and here allow the ribozyme to synthesise its own catalytic subunit ‘+’ and ‘–’ strands in segments and assemble them into a new active ribozyme.

scholarly journals Bridging the gap betweenin vitroandin vivoRNA folding

2016 ◽  
Vol 49 ◽  
Author(s):  
Kathleen A. Leamy ◽  
Sarah M. Assmann ◽  
David H. Mathews ◽  
Philip C. Bevilacqua
Keyword(s):  
Rna Structure ◽  
Rna Folding ◽  
Three Dimensional ◽  
Molecular Crowding ◽  
Cellular Processes ◽  
Cellular Environment ◽  
Folding Pathways ◽  
And Function

AbstractDeciphering the folding pathways and predicting the structures of complex three-dimensional biomolecules is central to elucidating biological function. RNA is single-stranded, which gives it the freedom to fold into complex secondary and tertiary structures. These structures endow RNA with the ability to perform complex chemistries and functions ranging from enzymatic activity to gene regulation. Given that RNA is involved in many essential cellular processes, it is critical to understand how it folds and functionsin vivo. Within the last few years, methods have been developed to probe RNA structuresin vivoand genome-wide. These studies reveal that RNA often adopts very different structuresin vivoandin vitro, and provide profound insights into RNA biology. Nonetheless, bothin vitroandin vivoapproaches have limitations: studies in the complex and uncontrolled cellular environment make it difficult to obtain insight into RNA folding pathways and thermodynamics, and studiesin vitrooften lack direct cellular relevance, leaving a gap in our knowledge of RNA foldingin vivo. This gap is being bridged by biophysical and mechanistic studies of RNA structure and function under conditions that mimic the cellular environment. To date, most artificial cytoplasms have used various polymers as molecular crowding agents and a series of small molecules as cosolutes. Studies under suchin vivo-likeconditions are yielding fresh insights, such as cooperative folding of functional RNAs and increased activity of ribozymes. These observations are accounted for in part by molecular crowding effects and interactions with other molecules. In this review, we report milestones in RNA foldingin vitroandin vivoand discuss ongoing experimental and computational efforts to bridge the gap between these two conditions in order to understand how RNA folds in the cell.

Transcription regulation through nascent RNA folding

2021 ◽  
pp. 166975
Author(s):  
Leonard Schärfen ◽  
Karla M. Neugebauer
Keyword(s):  
Transcription Regulation ◽  
Rna Folding ◽  
Nascent Rna
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