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Ancient Transcription Factors in the News.

ABSTRACT: In every cell from bacteria to mammals, NusG-like proteins bind transcribing RNA polymerase to modulate the rate of nascent RNA synthesis and to coordinate it with numerous cotranscriptional processes that ultimately determine the transcript fate. Housekeeping NusG factors regulate expression of the bulk of the genome, whereas their highly specialized paralogs control just a few targets. In Escherichia coli, NusG stimulates silencing of horizontally acquired genes, while its paralog RfaH counters NusG action by activating a subset of these genes. Acting alone or as part of regulatory complexes, NusG factors can promote uninterrupted RNA synthesis, bring about transcription pausing or premature termination, modulate RNA processing, and facilitate translation. Recent structural and mechanistic studies of NusG homologs from all domains of life reveal molecular details of multifaceted interactions that underpin their unexpectedly diverse regulatory roles. NusG proteins share conserved binding sites on RNA polymerase and many effects on the transcription elongation complex but differ in their mechanisms of recruitment, interactions with nucleic acids and secondary partners, and regulatory outcomes. Strikingly, some can alternate between autoinhibited and activated states that possess dramatically different secondary structures to achieve exquisite target specificity.

SUBMITTER: Artsimovitch I

PROVIDER: S-EPMC6391919 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Ancient Transcription Factors in the News.

Artsimovitch Irina I Knauer Stefan H SH

mBio 20190226 1

In every cell from bacteria to mammals, NusG-like proteins bind transcribing RNA polymerase to modulate the rate of nascent RNA synthesis and to coordinate it with numerous cotranscriptional processes that ultimately determine the transcript fate. Housekeeping NusG factors regulate expression of the bulk of the genome, whereas their highly specialized paralogs control just a few targets. In <i>Escherichia</i><i>coli</i>, NusG stimulates silencing of horizontally acquired genes, while its paralog ...[more]

PMID: 30808693

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Project description:BackgroundMammalian motor circuits display remarkable cellular diversity with hundreds of motor neuron (MN) subtypes innervating hundreds of different muscles. Extensive research on limb muscle-innervating MNs has begun to elucidate the genetic programs that control animal locomotion. In striking contrast, the molecular mechanisms underlying the development of axial muscle-innervating MNs, which control breathing and spinal alignment, are poorly studied.MethodsOur previous studies indicated that the function of the Collier/Olf/Ebf (COE) family of transcription factors (TFs) in axial MN development may be conserved from nematodes to simple chordates. Here, we examine the expression pattern of all four mouse COE family members (mEbf1-mEbf4) in spinal MNs and employ genetic approaches in both nematodes and mice to investigate their function in axial MN development.ResultsWe report that mEbf1 and mEbf2 are expressed in distinct MN clusters (termed "columns") that innervate different axial muscles. Mouse Ebf1 is expressed in MNs of the hypaxial motor column (HMC), which is necessary for breathing, while mEbf2 is expressed in MNs of the medial motor column (MMC) that control spinal alignment. Our characterization of Ebf2 knock-out mice uncovered a requirement for Ebf2 in the differentiation program of a subset of MMC MNs and revealed for the first time molecular diversity within MMC neurons. Intriguingly, transgenic expression of mEbf1 or mEbf2 can rescue axial MN differentiation and locomotory defects in nematodes (Caenorhabditis elegans) lacking unc-3, the sole C. elegans ortholog of the COE family, suggesting functional conservation among mEbf1, mEbf2 and nematode UNC-3.ConclusionsThese findings support the hypothesis that genetic programs controlling axial MN development are deeply conserved across species, and further advance our understanding of such programs by revealing an essential role for Ebf2 in mouse axial MNs. Because human mutations in COE orthologs lead to neurodevelopmental disorders characterized by motor developmental delay, our findings may advance our understanding of these human conditions.

Project description:Here, we generate a robust phylogenetic framework for the rRNA adenine N(6)-methyltransferase (RAMTase) protein family that shows a more ancient and complex evolutionary history within the family than previously reported. RAMTases occur universally by descent across the three domains of life, and typical orthologs within the family perform methylation of the small subunits of ribosomal RNA (rRNA). However, within the RAMTase family, two different groups of mitochondrial transcription factors, mtTFB1 and mtTFB2, have evolved in eukaryotes through neofunctionalization. Previous phylogenetic analyses have suggested that mtTFB1 and mtTFB2 comprise sister clades that arose via gene duplication, which occurred sometime following the endosymbiosis event that produced the mitochondrion. Through dense and taxonomically broad sampling of RAMTase family members especially within bacteria, we found that these eukaryotic mitochondrial transcription factors, mtTFB1 and mtTFB2, have independent origins in phylogenetically distant clades such that their divergence most likely predates the last universal common ancestor of life. The clade of mtTFB2s comprises orthologs in Opisthokonts and the clade of mtTFB1s includes orthologs in Amoebozoa and Metazoa. Thus, we clearly demonstrate that the neofunctionalization producing the transcription factor function evolved twice independently within the RAMTase family. These results are consistent with and help to elucidate outcomes from prior experimental studies, which found that some members of mtTFB1 still perform the ancestral rRNA methylation function, and the results have broader implications for understanding the evolution of new protein functions. Our phylogenetic reconstruction is also in agreement with prior studies showing two independent origins of plastid RAMTases in Viridiplantae and other photosynthetic autotrophs. We believe that this updated phylogeny of RAMTases should provide a robust evolutionary framework for ongoing studies to identify and characterize the functions of these proteins within diverse organisms.

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Ancient Transcription Factors in the News.

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Ancient Transcription Factors in the News.

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