Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Our mandala cover image reflects the ever-expanding complexity of eukaryotic transcriptional regulation, whose 50-year anniversary we celebrate in this special Focus issue.
Small RNAs guide nuclear Argonaute proteins to silence genomic target loci via recruitment of factors that lead to formation of repressive heterochromatin. Animal gonads use this pathway to repress transposable elements with PIWI-clade Argonaute proteins and their associated small RNAs called PIWI-interacting RNAs (piRNAs). Four research groups now identify a protein complex that acts as a molecular bridge between the piRNA pathway and the epigenetic silencing machinery.
Researchers have sought to understand the function and regulation of the motor protein dynein since its discovery more than 50 years ago1. Dynein-2 is one of the motors that move the intraflagellar transport (IFT) trains ― large protein complexes that are needed for the assembly and function of eukaryotic cilia and flagella. Toropova et al. report the single-particle cryo-EM structure of the human dynein-2 complex2, which unexpectedly reveals two different conformations of the motor subunit tails. One tail forms a zigzag that matches the periodicity of the IFT trains, which reinforces the auto-inhibition of dynein motor activity and the binding of multiple dynein-2 complexes along the train during anterograde transport.
The ‘N-end rule’ correlates the identity of the N-terminal residue of a protein to its in vivo half-life. A study has now shown that an N-terminal glycine can serve as a potent degradation signal, which reveals a novel branch of N terminus–dependent protein degradation.
AAA ATPases constitute a large family of molecular chaperones, many of which unfold substrate proteins. Two recent cryo-EM studies of the AAA ATPase Cdc48 capture this enzyme in the midst of protein unfolding and reveal a universal substrate-threading mechanism for ring-shaped ATPases.
James Kadonaga provides a retrospective of the biochemical analyses that demonstrated the role of chromatin in the regulation of RNA polymerase II transcription.
This personal Perspective by Joan and Ron Conaway describes the biochemical identification and characterization of three key transcription elongation factors, TFIIS, Elongin and ELL, and summarizes how the delineation of their functions has informed the understanding of the regulatory mechanisms that control elongation by RNA polymerase II.
This historical Perspective by John Lis summarizes the array of complementary biochemical, genetic, optical and genome-wide approaches that have enabled dissection of eukaryotic transcriptional mechanisms in their native, cellular environment, and considers the future insights offered by emerging technologies of ever-increasing sensitivity and resolution.
In this Review, Bob Roeder offers a personal, historical perspective of the landmark studies that elucidated the mechanism and regulation of eukaryotic transcription over five decades, from the initial discovery of three nuclear RNA polymerases to the structural, genomic and imaging approaches that continue to expand our understanding of the function of complex regulatory networks.
This review proposes an up-to-date, consensus thermodynamic model for the conformational changes associated with transport by the eukaryotic type I exporters from the ABC family and discusses structural insights into ABC transporter pharmacology.
Lewis and Lu present an approach using a rhodamine tag and a polarization microscope to follow 10°–16° rotation of an ɑ-helix, corresponding to 3.4- to 8.1-Å translation, from the MthK RCK domain in real time.
The energetics of Ca2+-dependent conformational changes in an RCK domain from MthK are now determined from real-time monitoring, leading to a model that predicts the channel’s open probability behavior.
The dynamics of conformational changes of an RCK domain of the MthK channel, combined with existing atomic structures of those states, allows the development of a mechanistic model for the channel.
Cryo-EM structure of the dynein-2 complex (involved in intraflagellar transport, IFT) reveals distinct conformations of the two DHC2 tails within the same assembly, suggesting the mechanisms of autoinhibition and of transport on anterograde IFT trains.
Cryo-EM structures of the multienzyme complex between the endoribonuclease Las1 and the polynucleotide kinase Grc3 reveal two molecular switches that coordinate nuclease and kinase function.
