PANDORA-seq Can Help Uncover Small RNAs

A team led by a biomedical scientist at the University of California, Riverside, has developed a new RNA-sequencing method PANDORA-seq (Panoramic RNA Display by Overcoming RNA Modification Aborted Sequencing) that can help discover numerous modified small RNAs that were previously undetectable. The study was published in Nature Cell Biology. 

It "PANDORA-seq can be widely used to profile small RNA landscapes in various physiological and disease conditions to facilitate the discovery of key regulatory small RNAs involved in these conditions," said QiChen, lead researcher. "Modified small RNAs wear an 'invisibility cloak' that prevents them from being detected by traditional RNA-sequencing methods. How many such modified RNAs are there? What is the origin of their sequences? And what exactly is their biological function? These are questions PANDORA-seq may be able to answer."

PANDORA-seq employs a stepwise enzymatic treatment to remove key RNA modifications, which then takes off the invisibility cloak used by the modified small RNAs. According to Chen, PANDORA-seq uncovers a surprising small-RNA landscape that is dominated by tsRNAs and rRNA-derived small RNAs, or rsRNAs, rather than microRNAs, which were previously believed to dominate many mammalian tissues and cells.

"With PANDORA-seq, we found unprecedented microRNA/tsRNA/rsRNA dynamics when somatic cells are reprogrammed to induced pluripotent stem cells, which are generated by adult cells and have properties similar to those of embryonic stem cells, making them capable of differentiating into all cell types of the body," said Sihem Cheloufi, co-corresponding author of the paper. "Some tsRNAs and rsRNAs can impact protein synthesis and even affect lineage differentiation in embryonic stem cells." Chen explained the current best-studied classes of small RNAs in mammals are microRNAs, which are abundant in mammalian somatic cells and control the kind and amount of proteins the cells make; and piRNAs, which are mainly expressed in the testis and modulate germ cell development.