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NON-CODING RNAS: THE DARK MATTER OF OUR GENOMES

Our genetic information is encoded mainly in the biochemical sequence of DNA and forms our 3-billion-base-long genome. RNA, which is similar to DNA, is produced based on this genomic information. In humans, less than 3% of the genomic information is transferred into a type of RNA called messenger RNA (mRNA). Through mRNA this small but most studied fraction of the genome is coding for proteins, i.e. is used to produce the chemical molecules that have been believed to enable most biological processes until now (protein-coding genome). However, it is the non-coding genome that holds the lion’s share, that ~97% of the human genomic sequence that has been until recently called ''junk'' DNA and considered to have no functional importance.

To store the extraordinary amount of genomic information in non-digital media we would need more than 150 hefty telephone books; until recently more than a day would have been needed to “read” just a single page of these books. Today, a new generation of sequencers can read all these pages in a matter of hours, enabling us for the first time to take a closer look at the complex architecture of our genome and, of all, of its non-coding part. Novel sequencing technologies have revealed that >80% of the noncoding genome is transcribed into non-coding RNAs (ncRNAs). The function of most of them and their role in human disease remains largely unknown.

All the RNAs available in a cell are collectively referred as the cell’s transcriptome, the study of which is referred as RNA Genomics and uses, among others, RNA Bioinformatics algorithms. The Zovoilis Lab uses next generation sequencing and bioinformatics algorithms to shed light on the non-coding genome and transcriptome and advance our knowledge of the human genome’s dark matter.

Four types of non-coding RNAs are the main focus of our Lab:
i) non-coding RNAs near promoters, splicing and transcription termination sites of the genes,
ii) non-coding RNAs originating from repetitive elements,
iii) chimeric RNAs derived from fusion of different non-coding RNA transcripts, and
iv) circular non-coding RNAs.

Among these non-coding RNAs our Lab seeks candidates that regulate the cell’s response to stress. We study variations in these non-coding RNAs that may be responsible for impaired response to stress during aging. Dissecting the role of these RNAs will help us understand their function in human and their importance in aging-associated diseases, such as cancer and dementia, which are connected to impaired response to cellular stress.