A small conditional RNA (scRNA) is a small

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

molecule or complex (typically less than approximately 100 nt) engineered to interact and change conformation conditionally in response to cognate molecular inputs so as to perform

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

in vitro, in situ, or in vivo. In the absence of cognate input molecules, scRNAs are engineered to coexist metastably or stably without interacting. Detection of the cognate inputs initiates downstream conformational changes of one or more scRNAs leading to generation of the desired output signal. The output signal may be intended to read out the state of

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

biological circuitry (e.g., mapping

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

for biological research or medical diagnosis), or to regulate the state of endogenous biological circuitry (e.g., perturbing gene expression for biological research or medical treatment). scRNA sequences can be programmed to recognize different inputs or to activate different outputs, achieving even single-nucleotide sequence selectivity. scRNA signal transduction exploits principles from the emerging disciplines of dynamic RNA nanotechnology, molecular programming, and synthetic biology.

Examples of scRNA signal transduction

Fluorophore-labeled scRNAs have been engineered to transduce between detection of mRNA targets and generation of bright fluorescent amplification polymers in situ (Figure 1). In this context, scRNA signal transduction enables multiplexed mapping of mRNA expression within intact vertebrate embryos (Figure 2). scRNAs have been engineered to perform shape and sequence transduction to conditionally produce a Dicer substrate targeting 'silencing target' mRNA Y upon detection of an independent 'detection target' mRNA X, with subsequent Dicer processing yielding a small interfering RNA ( siRNA) targeting mRNA Y for destruction (Figure 3). In this context, scRNA signal transduction provides a step towards implementing conditional RNA interference (Figure 4).

Conditional Dicer substrate formation via shape and sequence transduction with scRNAs

Design elements

scRNAs can be engineered to exploit diverse design elements: *scRNA reactants may be metastable or

stable A stable is a building in which livestock, especially horses, are kept. It most commonly means a building that is divided into separate stalls for individual animals and livestock. There are many different types of stables in use today; the ...

*scRNA signal transduction cascades can be catalytic or non-catalytic *scRNAs can nucleate with each other or with input or output molecules via toehold/toehold nucleation, loop/toehold nucleation, or template/toehold nucleation *scRNAs can dissociate with each other or with input or output molecules via 3-way branch migration, 4-way branch migration, or spontaneous dissociation *scRNA reactants can be monomers, dimers, or other multimers

References

{{reflist, refs= {{cite journal, title=Conditional Dicer substrate formation via shape and sequence transduction with small conditional RNAs, doi=10.1021/ja404676x , volume=135, issue=46, journal=Journal of the American Chemical Society, pages=17322–17330, vauthors = Hochrein LM, Schwarzkopf M, Shahgholi M, Yin P, Pierce NA , pmid=24219616 , pmc=3842090, year=2013 {{cite journal, title=Programmable in situ amplification for multiplexed imaging of mRNA expression, volume=28 , issue=11 , journal = Nature Biotechnology, pages=1208–1212, year= 2010, vauthors = Choi HM, Chang JY, Trinh LA, Padilla JE, Fraser SE, Pierce NA , doi=10.1038/nbt.1692, pmid=21037591 , pmc=3058322 {{cite journal, title=Exquisite sequence selectivity with small conditional RNAs , vauthors = Sternberg JB, Pierce NA , doi=10.1021/nl501593r , volume=14, issue = 8 , journal=Nano Letters, pages=4568–4572 , pmid=24979041 , pmc=4134187, year = 2014 , bibcode = 2014NanoL..14.4568S Molecular genetics Non-coding RNA