Perspectives

The use of nanodiscs is substantially fostering structural and functional studies of membrane protein. This Perspective summarizes the recent use of nanodiscs as an invaluable tool for the characterization of membrane proteins.

This Perspective provides an overview of recent progress, successes, challenges and future opportunities in the application of solution NMR and solid-state NMR methods to study the structure, dynamics and function of membrane proteins.

This Perspective discusses how two complementary approaches, bottom-up in vitro and top-down in situ structural biology, have now converged to generate the first predictive structural models of the nuclear pore scaffold.

This Perspective highlights recent progress on the location, functions and mechanisms of N⁶-methyladenosine (m⁶A), the most abundant internal modification in eukaryotic mRNA. In particular, the authors discuss how m⁶A modification affects the mammalian RNA life cycle at multiple stages.

In this Perspective, the authors discuss how recent innovations in single-molecule fluorescence approaches now permit protein dynamics to be monitored in increasingly complex biological systems and cellular environments.

Transcription of telomeres generates long noncoding RNAs (lncRNAs) composed of telomeric repeat sequences (TERRA) that hybridize with telomeric DNA and are components of telomeric heterochromatin. This Perspective considers the physiological roles of TERRA in telomere homeostasis and proposes that TERRA's functions are determined by the state of its telomere targets.

Telomerase recruitment and activity are regulated by telomere-bound proteins that protect the chromosome ends. In this Perspective, the authors discuss recent advances in understanding how the interactions of shelterin and telomerase components contribute to telomere-length homeostasis.

New methods permit genomic mapping of oxidized methylcytosines at single-base resolution and suggest new regulatory functions for 5-methylcytocine (5mC) derivatives 5hmC, 5fC and 5caC in the mammalian genome.

In this Perspective, Spitale, Chang and Chu discuss recent technological advances that will aid in the functional characterization of long noncoding RNAs, which up to now has posed a substantial challenge.

Emerging evidence from genome-wide analyses reveals that DNA methylation, an epigenetic modification associated with the repression of gene expression, can also promote transcriptional activation.

DNA replication begins with prereplication-complex formation at origins and is followed by helicase activation to unwind DNA at the replication fork. This Perspective compares bacterial DnaB and eukaryotic MCM2–7 helicase-loading mechanisms and discusses emerging data supporting current models of how two MCM2–7 complexes are loaded to form a double hexamer.

SIMIBI-type NTP-binding proteins are an ancient subfamily of nucleotide-binding proteins that comprises both dimeric ATPases and GTPases (SIMIBI 'twins'). This Perspective focuses on a subset of SIMIBI proteins with a defined function in protein targeting and localization, and aims to define common mechanistic principles and differences for these proteins.

Whereas post-translational modifications (PTMs) in histone tails are well characterized, functional and mechanistic insights into PTMs in the globular nucleosome core have been lacking. This Perspective covers recent advances in the understanding of lateral-surface PTMs and their effects on nucleosome and chromatin dynamics.

Cells have evolved so-called mRNA surveillance mechanisms to monitor mRNAs as they are translated and to degrade troublesome transcripts. Studies of mRNA surveillance have traditionally focused on mRNA fate. In this Perspective, the authors explore mRNA surveillance from the viewpoint of its origins on the ribosome, which should lead to new and unanticipated insights that inform future studies.