Riken Omics Center from Japan presents a well-crafted animation that summarizes one of the most important subjects of biology since 1958. The central dogma is our first systematic approach in understanding nature of the information flow and manufacture of structures within a living cell. The viewer must be warned that the structures in this animation are artistic representations and in reality they look quite different from space ships. For example RNA Polymerase II is one of the most well-studied enzymes with a complicated structure made up by assembly of 12 subunits in eukaryotic organisms.
“The operative industry of Nature is so prolific that machines will be eventually found not only unknown to us but also unimaginable by our mind.” — Marcello Malpighi (1628–1694) – De Viscerum Structura (1666).
The year 2012 marked the centennial of the discovery of X-ray chrystallography by the Australian phycisist William Lawrence Bragg. He shared the Nobel Prize with his father in 1915. The technique was so powerfull that since its discovery, it generarated 28 Nobel Prizes including the discovery of DNA. Thanks to X-ray chrystallography today we know the structures of complex molecules such as insulin, vitamin B12 or hemoglobin with great precison. Mars rover Curiosity has X-ray diffraction capability analyzing Martian soil samples.
The animation starts with a slow travel from the cytoplasm into the nucleus and then shows the condensed form of the DNA molecule residing on a chromosome. The condensed DNA is wrapped around histone molecules keeping the inactive regions of the chromosomes neat and tidy.
It then shows the uncoiled DNA where a gene is going to be transcribed. Transcription of the gene into a messenger RNA requires transcription factors. DNA binding transcription factor proteins are the key initiators of this process: they help assembly of the RNA Polymerase II around the promoter regions marking beginning of the genes. Just like a sprinter positioning on a running block before a race, these transcription factors help positioning of the RNA Polymerase II around control regions of DNA called promoters located upstream of the gene. Promoters interact with enhancers found further away from the genes increasing the complexity of transcriptional control of a gene. The following video illustrates major steps of RNA polymerase II enzyme transcribing a gene produced by Patrick Cremer’s lab in Ludwig Maximilians University at Munich (video has no narration):
Following transcription, the messenger RNA (mRNA) is edited through a mechanism called splicing. Splicing reactions are carried out at distinct centers called spliceosomes by a group of non-coding small RNA called small nuclear RNA (snRNA). There’s also another group of small non-coding RNA small nucleolar RNA (snoRNA) which are almost entirely restricted to ribosome biogenesis and should not be confused with snRNAs. The video below articulates the splicing of an mRNA that removes three introns – the non-coding sections of the mRNA molecule (animation from Cold Spring Harbor Laboratories, Dolan DNA Learning Center):
Once mRNA is spliced it is further packaged by proteins that contain nuclear export signals in order to be exported out of the nucleus. Except transfer RNAs and small RNAs who can be “naked”, no other RNA can exit the nucleus without these proteins. Nuclear pore complexes which serve as selective gates between the nucleus and the cytoplasm recognize nuclear export signal carrying proteins and let mRNA exit into the cytoplasm. The following video provides a structural rendering of the Nuclear Pore Complex produced by Samir S. Patel of the Rexach Lab from University of California Santa Cruz:
Once in the cytoplasm, ribosomes assemble around messenger RNA and facilitate translation into protein. Energetically protein translation consumes many orders of magnitude more energy than transcription. Although RNA transcription has 3 times more units to process (three nucleotides form a codon), protein translation needs charged transfer RNAs and each messenger RNA can be read by the ribosome many many times making translation more energy consuming.
Many organisms including bacteria, fungi and some plants by-pass Central Dogma by synthesizing short proteins called peptides through impressively massive enzymes without using ribosomes, mRNA and even genetically encoded information on the DNA. These enzymes are called non-ribosomal peptide synthetases which produce a dazzling array of very potent aminoacid-based secondary metabolites including antibiotics, toxins, pigments and metal-sequestering compounds. Non-ribosomal peptides are produced from a wide array of modified amino acids that are not limited to the 20 universal types used in ribosomal translation increasing the diversity of chemicals living bodies can manufacture.
After all the molecular videos it is impossible to resist from posting this amusing video about the ENCODE project which is built on our knowledge of the central dogma: