One Gene-One Peptide Hypothesis was a bold statement proposed by Edward Tatum and George Beadle in 1941 heralding the nascent field of molecular genetics. The proposal was long before we knew anything about the nature and structure of the DNA. It was rather vague how a gene encoded a protein. The Central Dogma of biology was coined by Francis Crick in late 1950s but the intermediate molecule known as the messenger RNA was identified (?) in 1960 by Arthur Pardee, Francois Jacob and Jacques Monod. Although hugely important for understanding life, the discovery of messenger RNA did not produce a Nobel Prize. Many dozens of people independently contributed to the knowledge pool and it is rather difficult to make an attribution to a specific group of people for its discovery.
In 1977 an unexpected discovery by Sue Berget revealed that mRNA and its corresponding gene region in DNA didn’t match. When they hybridized there were curious bulges indicating presence of some extra sequences. Again in 1977 Rich Roberts also reached same conclusion through independent experimentation. Discovery of “split genes” would lead to Nobel Prize in 1993. In 1978, sections of the split genes were named intron (intragenic) and exon (expressed) by Wally Gilbert. Although the initial discovery of intron/exon regions was made on adenovirus the split nature of genes is widespread across the tree of life.
The interrupted architecture of genes led biologists to explore this new layer of complexity in the Central Dogma of biology. Biologists began to question the evolution of introns. Are they a relic of the past RNA World? Are they increasing because of some yet undiscovered quirk of nature? Do introns have adaptive significance? The questions still remain unresolved as the multi-decadal introns first vs. introns late debate still continues today.
Associations between hundreds of human diseases and pre-messenger RNA splicing.
This molecular visualization by N Molecular Systems introduces the details of the cellular machinery which carries out splicing. The visualization explores the structure of a spliceosome at 3.6-angstrom resolution, solved by the Shi Yigong group of Tsinghua University. It compares spliceosome with another catalytically active RNA complex, the ribosome. Then it lays out the sequential series of events with participating subunit complexes that eventually folds pre-mRNA into a lariat structure so that the intronic regions gets edited out by splicing. The visualization also introduces peripheral complexes that aid the core spliceosome. Comparison of catalytic centers between the spliceosome and self-splicing group II intron is also quite informative to see the ancestral relationships and understand the evolution of gene splicing. Visualization includes a brief discussion of shared common ancestry with mobile genetic elements.
Scientific Visualization
Dan W. Nowakowski, Ph.D.
Producers
Yan Liang, Ph.D.
Dan W. Nowakowski, Ph.D.
RNA Splicing by the Spliceosome from Nature Documentaries on Vimeo.
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