40 years ago "The Cerebellum as a Neuronal MACHINE" - and now "The Human Genome: RNA MACHINE" to a theorist represent similar challenges. The stage is grand for mathematical and information-theoretical breakthroughs. Clearly, the "hundreds of thousand if not millions of 'genes'" can not be the same as the "~20,000 protein-coding 'genes'". The distinction between the two different definitions of the two terms "genes" in one sentence will keep theorists busy, especially in the context of the "RNA-based network of complex organisms". The concept of "Junk DNA" is gone. New concepts uniting the biology and informatics sides of Post-ENCODE Genomics will help eradicate "Junk DNA diseases". The sooner, the better.