Argonaute: Roles in Yeast and Human
In yeast, the function and mode of action of nuclear RNAi are well documented. Contrarily, the roles of mammalian nuclear RNAi are controversial. Mammalian Argonaute, a central protein component in small RNA silencing pathways, was recently shown to have a role in alternative splicing by a yet elusive molecular mechanism. In this issue of Transcription, Harel-Bellan et al. discuss the human nuclear RNAi mechanism in light of what is known of the yeast process.
Mesp1 and the Cardiac Cell Fate
In this issue of Transcription, Liu and Schwartz discuss the role of Mesp1 in the programming of human cells into cardiomyocytes. Mesp1 is recognized as the first sign of the cardiac lineages out of the nascent mesoderm and is regulated by stem cell factor Oct4, early gastrulation signal canonical Wnts and two T-box factors, T and Eomes. In conjunction with other transcription factors, Mesp1 programs/reprograms human cells toward cardiomyocytes.
Cryptic Transcription
The eukaryotic chromatin structure is essential in correctly defining transcription units. Impairing this structure can activate cryptic promoters, and lead to the accumulation of aberrant RNA transcripts. In this issue, Hennig and Fischer discuss critical pathways that are responsible for the repression of cryptic transcription and the maintenance of genome integrity.
Gene Expression in the Brain
Wang and Konopka explore recent discoveries, using comparative genomics in human and non-human primate brain, on the evolution of higher cognitive functions in humans. The authors put this knowledge into context with biological phenotypes and diseases in humans.
Transcription-Coupled Repair
Transcription-coupled repair (TCR) is one of the key nucleotide excision repair pathways required to preserve genome integrity. In this issue of Transcription, Monnet et al. review recent single-molecule experiments that have studied the initial steps of TCR and discuss new perspectives.
On the Roles of H2A/H2B-Like Proteins
Core histones are the most highly conserved proteins in eukaryotes. The related “deviant” histones share the histone-fold domain, and serve various roles in DNA metabolism. Gnesutta et al. present in this issue of Transcription a structural and functional outlook of H2A/H2B-like deviant histones in transcription, replication and remodeling.
TFIID’s Conformation Transitions and Promoter Binding
Structural studies have recently revealed that modular interactions underlie TFIID’s ability to bind simultaneously multiple promoter motifs and to define a DNA state that will facilitate transcription initiation. Cianfrocco and Nogales propose a general model of promoter binding by TFIID, where co-activators, activators, and histone modifications promote and/or stabilize a conformational state of TFIID that results in core promoter engagement. The authors propose that TFIID’s extensive interaction with promoter DNA leads to topological changes in the DNA that facilitate the eventual loading of RNAP II.
Transcriptional Stalling in B-Lymphocytes
B cells undergo controlled DNA mutation in order to generate a variety of antigen-specific antibodies. B cells utilize three DNA alteration strategies—V(D)J recombination, somatic hypermutation (SHM) and class switch recombination (CSR)—to somatically mutate their genome. The single-strand DNA cytidine deaminase, AID, is responsible for SHM and CSR. A review article by Sun et al. discusses recent findings that point toward various components of RNAP II “stalling” machinery as regulators of AID activity during antibody diversification and maintenance of B cell genome integrity.
Translocation and Fidelity of Escherichia coli RNA Polymerase
In this issue of Transcription, Nedialkov and Burton studied Escherichia coli RNA polymerase (RNAP) ternary elongation complex (TEC) using exonuclease III (exo III) mapping. The authors show that in the absence of NTPs, RNAP appears to stall primarily in a post-translocated state and to return slowly to a pre-translocated state. Exo III mapping, therefore, appears inconsistent with an unrestrained thermal ratchet model for translocation, in which RNAP freely and rapidly oscillates between pre- and post-translocated positions. As the post-translocated TEC can be strongly stabilized by NTP addition, the authors ranked NTP analogs for their ability to preserve the post-translocation state, giving insight into RNAP fidelity. Effects of NTPs (and analogs) and analysis of chemically modified RNA 3′ ends demonstrate that patterns of exo III mapping arise from intrinsic and subtle alterations at the RNAP active site, far from the site of exo III action.