The Old and New Testaments of gene regulation

Abstract

I relate a story of genesis told from the point of view of multi-subunit RNA polymerases (RNAPs) including an Old Testament (core RNAP motifs in all cellular life) and a New Testament (the RNAP II heptad repeat carboxy terminal domain (CTD) and CTD interactome in eukarya). The Old Testament: at their active site, one class of eukaryotic interfering RNAP and ubiquitous multi-subunit RNAPs each have two-double psi β barrel (DPBB) motifs (a distinct pattern for compact 6-β sheet barrels). Between β sheets 2 and 3 of the β subunit type DPBB of all multi-subunit RNAPs is a sandwich barrel hybrid motif (SBHM) that interacts with conserved initiation and elongation factors required to utilize a DNA template. Analysis of RNAP core protein motifs, therefore, indicates that RNAP evolution can be traced from the RNA-protein world to LUCA (the last universal common ancestor) branching to LECA (the last eukaryotic common ancestor) and to the present day, spanning about 4 billion years. The New Testament: in the eukaryotic lineage, I posit that splitting RNAP functions into RNAPs I, II and III and innovations developed around the CTD heptad repeat of RNAP II and the extensive CTD interactome helps to describe how greater structural, cell cycle, epigenetic and signaling complexity co-evolved in eukaryotes relative to eubacteria and archaea.

tRNA structure and evolution and standardization to the three nucleotide genetic code

“…From these other studies, we were cognizant that in ancient evolution repeating sequences and motifs often generated the most lasting biologic complexity. Sometimes pseudo symmetry results from repeats, as in the case of protein barrels or pseudo-dimeric folds, as in (β−α) 8 barrels, 15 cradle loop barrels (i.e., RIFT barrels and double-Ψ−β-barrels; ββαβ repeats) (including RNA polymerases of the two double-Ψ−β-barrel type) 15 , 16 and TATA-binding protein (a pseudo-dimer of two TBP folds). The Rossmann fold is a twisted linear (β−α) 8 sheet possibly rearranged from a (β−α) 8 barrel.…”

“…The Rossmann fold is a twisted linear (β−α) 8 sheet possibly rearranged from a (β−α) 8 barrel. 15 Archaeal TFB (transcription factor B; related to eukaryotic TFIIB) includes two helix-turn-helix repeats. Bacterial sigma transcription factors are homologs of archaeal TFB and evolved from a ≥four helix-turn-helix repeat.…”

Flexibility–rigidity index for protein–nucleic acid flexibility and fluctuation analysis

“…RNA polymerase is one of the essential enzymes for all life on Earth as we know it today and possibly from the very beginning of life . Despite this importance, the mechanisms for many of the polymerase's functions are still not well understood on the atomic level.…”

“…Anisotropic FRI for conformational motion prediction of an RNA polymerase RNA polymerase is one of the essential enzymes for all life on Earth as we know it today and possibly from the very beginning of life. [7,25] Despite this importance, the mechanisms for many of the polymerase's functions are still not well understood on the atomic level. Considerable effort has been spent both experimentally and computationally to understand RNAP polymerase function in more detail but many questions remain.…”

Archaea, from obscurity to superhero microbes: 40 years of surprises and critical biological insights

“…These archaeal homologues frequently prove to be more experimentally tractable than the more complex and less stable eukaryotic counterparts, and this is reflected by the several thousand archaeal protein X-ray crystal structures that have been deposited to the Protein Data Bank (PDB). Indeed, structural studies of the archaeal homologous of a wide variety of macromolecular assemblies including the RNA polymerases [23], DNA replication machineries [19], ribosomes [24], proteasomes [25] and chaperonins [26] have all led to advancements in our understanding of the parallel processes in complex eukaryotic cells.…”