CircRNAs as regulators of transcriptome lifespan and cellular viability

RNA has long been known as a crucial molecule of life, but only recently has it been considered as a key to the regulation of cellular processes. The dynamic development of new chemical and biological tools has allowed researchers to recognize the variety of RNAs in living cells, as well as over 140 possible RNA modifications. CircRNAs are one of these newly discovered RNA families for which both detailed structure and functions require further investigation. Recent worldwide global research has led to the discovery of intriguing functions of circRNAs such as encoding of protein, inducting innate immunity genes and sponging small RNAs. To date, most interactions of circRNAs with small RNAs are considered in the sequential not structural, context. We will determine the structural context and epitranscriptomic profile of neuronal circRNAs to better understand their interactions with other molecules in the living cell. We apply the photo-caging and photo-crosslinking procedures for real-time tracking of the RNA dynamics in order to analyze their impact on cell differentiation and viability. Our research will shed light on thedynamics of circular RNAs structure and allow to understand their mode of action, and function as a potential information carrier.

In search of new small RNA families

The commonly analyzed pool of RNAs called the “transcriptome” consists of RNA molecules longer than 15-18 nucleotides. Because of precipitation-based RNA isolation protocols, we lose a fraction of ultra-small RNAs (usRNAs). To date this mysterious groups of RNAs has not been characterized and its biological roles remain unknown. At the same time, researchers focused on the small interfering RNAs have demonstrated that with as short as 8 nt, direct hybridization with mRNA (the seed region) may result in translation inhibition. We hypothesize that existing usRNAs, as well as interfering RNAs, may play regulatory roles in long lifespan of RNAs. We will take on the challenge of isolating and sequencing of “dark matter” of the transcriptome – ultra-small RNAs. We investigate the regulatory role of usRNAs in neuron development and survival. The scope of our work to characterize a new class of usRNAs will lead to better understanding of RNA processing and degradation in cell.

RNA-based therapeutic approaches to Parkinson’s disease

To propose a new therapeutic approach for Parkinson’s disease, we need to understand the etymology of neurodegeneration. Very little is known about where and why the neuronal degradation starts. However, we know that the key to cellular homeostasis and survival is communication. Lately, some circular and small RNAs have been discovered enriched and in stable form in neuronal exosomes. These small cell-derived vesicles are produced by cells and transported in many eukaryotic fluids. In our investigation, we focus on the role of long RNAs as a carrier of information and small RNAs as modulators of circRNAs. We examine a pool of exosomal RNAs to identify transcriptomic marks of cellular processes such as aging and neurodegeneration. This work will help to understand the potential function of RNAs in intercellular signaling and their link with progressive neurodegeneration.