Researchers from the Spanish National Cancer Research Center’s Structural Computational Biology Group are making a huge catalog of chimeric RNAs available to the public domain. Specifically, the new database holds over 29,000 small RNA molecules that originate from different genomic regions, hence the term chimeric RNA. The scientists believe these molecules could reveal useful markers for the clinical oncology practice, and even novel drug targets for cancer treatment.
Their paper (“ChiTaRS 2.1: an improved database of the chimeric transcripts and RNA-seq data with novel sense-antisense chimeric RNA transcripts”) appears in Nucleic Acids Research (NAR), and the data can be found in the ChiTaRs database.
Chimeric proteins can be produced through two very different molecular processes. One is via chromosomal translocation and the other takes place in a less well-known process where RNAs originating from different genes combine to create a single protein. Although not much is known about the function of chimeras in cells, “we know they play an important role in cancer,” points out Valencia Alfonso, Ph.D., who led the research team. In fact, chromosomal translocations serve as markers for some types of tumors such as chronic myeloid leukemia.
The new catalog, whose starting point was the bioinformatics analysis of thousands of chimeras described in the literature, is made up of chimeric RNAs derived from eight different species including humans, mice, and fruit flies or yeast. “This phenomenon happens throughout evolution [it is already present in yeast, whose evolutionary origin differs from that of humans by millions of years], although we know very little about it given that, very often, chimeric RNAs are expressed at low levels in cells,” adds Dr. Alfonso.
Part of the biocomputing and bioinformatics data has been verified by laboratory experiments. Up to 297 chimeras have been detected in three human cell lines, of which 69 had not been described in humans until now: these proteins originate from the two strands of DNA (those with opposite reading direction) that belong to the same gene.
“The ChiTaRS-2.1 database is designed to advance the field of cancer research as well as our understanding of the phenomenon of chimeric transcripts and its evolution in eukaryotes,” wrote the investigators.
“The future of the research lies in understanding the relevance of all of these processes to normal cell maintenance and its contribution to the genome and cancer biology studies. The RNAs and chimeric proteins have become a focal point of attention over the last few years, given that they can be used as new tumor markers, as well as potential targets for the generation of new drugs,” says Milana Frenkel-Morgenstern, Ph.D., the first author of the study.