When geneticist Barbara McClintock discovered “jumping gene” 60 years ago, biologists were skeptical about the discovery and even laughed at McClintock’s theory. What they did not expect was that “jumping gene”, now known as transposon element, which seems “nonsense”, makes up about 50% of the human genome playing essential roles in DNA repair, gene regulation, and maintaining genetic diversity. As always, we are stunned by new discoveries in nature. There is only 1% of the human genome that contains protein-coding genes, the rest was regarded as “junk DNA” previously until the discovery of tRNA, rRNA, siRNA and other RNA species which play essential roles in human physiology. Only until recently, long non-coding RNA (lncRNA) starts to get under the spotlight as they are starting to be studied more recently with secrets gradually unfolding.
Those lncRNA molecules, which are more than 200 nucleotides in size, are tissue- and cellular state-specific, so they serve well as signals of cellular programs which could potentially identify cellular pathologies such as cancer, providing prognostic value or giving therapeutic advice to cancer patients (Figure 1). Tools could be developed for these application. Being used as biomarkers is not their only application. lncRNAs in the nucleus often regulate gene transcriptions, chromatin looping and gene methylation, etc. They are also able to regulate distant genes through modulation of transcriptional factor recruitment, chromatin modification, and serving as a scaffold for assembly of multiple regulatory molecules. In the cytoplasm, lncRNAs may modulate protein functions, regulate protein-protein interactions, or even direct localization within cellular compartments. Moreover, some cytoplasmic lncRNAs are able to control mRNA stability, splicing and translation. In the context of cancer, lncRNAs may play roles in cancer cell proliferation, growth inhibition, viability, and motility, implying they could be attractive targets for cancer treatment. As the understanding of these lncRNA advances, it is possible to target the same cancer-promoting pathway from multiple angles and it could potentially reduce treatment resistance and improve therapeutic outcome.
Figure 1. Cancer-associated IncRNAs (Schmitt and Chang, 2016)
How many other “junks” are out there? All above discoveries continuously encourage researchers to never overlook research results that cannot be comprehended with our current knowledge base, but to dig deeper and discover the true treasure buried behind.
