VISITING SPEAKER: RNA rules!

It appears that the genetic programming of humans and other complex organisms has been fundamentally misunderstood for the past 50 years, because of the assumption that most genetic information is transacted by proteins. The human genome contains about 20,000 conventional protein-coding genes, surprisingly about the same number and with largely similar functions as those in tiny worms that have only 1000 cells. On the other hand, the extent of non-protein-coding DNA, traditionally thought to be junk, increases with increasing complexity, reaching over 98.8 percent in humans. Moreover, it is now evident that these non-coding sequences are transcribed in a dynamic manner, to produce tens, if not hundreds of thousands of noncoding RNAs, and that most complex genetic phenomena are RNA-directed, which suggests that there exists a vast hidden layer of regulatory RNAs that control human development and brain function. We have recently demonstrated that the majority of long noncoding RNAs are expressed in precise cellular and subcellular locations in the brain, that a subset of noncoding RNAs are dynamically regulated during the differentiation of embryonal stem cells, neural stem cells, immune cells and muscle, as well as in cancer, and that some of these RNAs are essential components of subnuclear structures or complexed with particular types of activated chromatin. We have also identified new classes of tiny RNAs associated with transcription start sites and splice sites, and shown that protein-coding sequences are preferentially located in nucleosomes, which provides a platform for epigenetic control of gene expression and transcript structure. We have also found that conventional protein-coding mRNAs can also be processed to produce regulatory RNAs, and that RNA is the plastic substrate for epigenome-environment interactions. The outcomes of our research will be to expand our understanding of human evolution, development, brain function and disease.