Naturally occurring nucleic acid nano-devices
We are also interested in understanding naturally occuring nucleic acid based devices such as non-coding RNAs. RNA is an exciting and powerful biological medium for making genetically encoded, synthetic nucleic acid architectures that can probe and program the cell.
Chakraborty, S., Mehtab, S., Krishnan, Y.* The predictive power of synthetic nucleic acid technologies in RNA biology. Accounts of Chemical Research, 2014 , 47, 1710-1719
Several naturally occuring nucleic acid based devices are nearly entirely composed of RNA: riboswitches, ribozymes and long non-coding RNAs to name a few. We also want to understand how some of these RNA based devices function, in the hope that we may someday be able to use the lessons learned to engineer smarter synthetic devices. MicroRNAs for example, are a class of RNAs that control gene expression by either by RNA transcript degradation or translational repression. Expressions of miRNAs are highly regulated in tissues, disruption of which leads to disease. But how this regulation is achieved and maintained is still largely unknown. MiRNAs that reside on clustered or polycistronic transcripts represent a more complex case where individual miRNAs from a cluster are processed with different efficiencies despite being co-transcribed. To shed light on the regulatory mechanisms that might be operating in these cases we considered the long polycistronic primary miRNA transcript pri-miR-17-92a that contains six miRNAs with diverse function. The six miRNA domains on this cluster are differentially processed to produce varying amounts of resultant mature miRNAs in different tissues. How this is achieved is not known. We show using various biochemical and biophysical methods coupled with mutational studies that pri-miR-17-92a adopts a specific three dimensional architecture which poses a kinetic barrier to its own processing. This tertiary structure could create suboptimal protein recognition sites on the pri-miRNA cluster due to higher order structure formation.
Chakraborty, S., Mehtab, S., Patwardhan, A.R., Krishnan, Y.* Pri-miR-17-92a transcript folds into a tertiary structure and autoregulates its processing. RNA, 2012, 18, 1014-1028