RNA folding dynamics and RNA engineering
We investigate the design principles of functional RNA sequences. We address this issue by developing conceptual, computational and experimental methods that take into account the folding dynamics of RNA, and by applying our approach to the analysis of natural regulatory RNA sequences and to the design of synthetic RNA switches.
RNA is an essential and versatile component of biological systems. RNA sequences can fold in complex structures to perform active biological functions or to serve as structural scaffold in numerous biological processes.
Because the folding of an RNA molecule occurs while it is synthesized by the RNA polymerase, RNA folding is inherently a dynamical and hierarchical sequence of events, where the final structure is determined by the structural intermediates and structural rearrangements explored by the elongating RNA molecule during its synthesis.
Yet, the impact of this co-transcriptional folding process on the folding and function of RNA sequences is rarely taken into account in sequence analyses or when RNA molecules are engineered for functional purpose.
How is encoded in its nucleotide sequence the folding path that guides an RNA molecule towards its final functional structure ? We address this fundamental question of the link sequence-folding-function in RNA using a learning-by-designing approach. We investigate design principles of RNA folding by analyzing and engineering functional RNA sequences while explicitly taking into account the co-transcriptional and dynamical nature of the RNA folding process. Further, we apply our approach to the design of synthetic RNA switches.
Hervé Isambert – Institut Curie (Paris, France)
Bianca Mladek – Max F. Perutz Laboratories & University of Vienna (Austria)
Hans Geiselmann – LIPhy (Grenoble, France)
- RNA synthetic biology inspired from bacteria : construction of transcription attenuators under antisense regulation
A. Dawid, B. Cayrol, H. Isambert
Physical Biology 6, 025007 (2009)
- A nanostructure made of a bacterial noncoding RNA
B. Cayrol, C. Nogues, A. Dawid, I. Sagi, P. Silberzan, H. Isambert
J. Am. Chem. Soc. 131, 17270-6 (2009)