Brief Communications in 2012

Adenosylcobalamin is a form of vitamin B₁₂ that serves as a coenzyme in different reactions and as a ligand for riboswitches to control bacterial gene expression. The crystal structure of a B₁₂ riboswitch from Symbiobacterium thermophilum bound to its ligand adenosylcobalamin is now presented, revealing the determinants for ligand recognition and gene expression control.

A systematic in vitro analysis of five different forms of cytosine in mammalian and yeast RNA polymerase II (Pol II) transcription demonstrates that Pol II can read and distinguish subtle differences in modified cytosines and process them differently, suggesting a putative functional interplay between cytosine modification status and transcription.

The assembly of diverse immunoglobulin genes results in part from Rag protein–mediated DNA double-strand breaks at the edges of immunoglobulin gene segments, followed by the combinatorial reassembly of these segments. A transposase from the insect Helicoverpa zea is now shown to be active in vitro, and its breakage and joining activities resemble those of Rag, suggesting a common progenitor.

STING is an important component of the innate immune system involved in the direct response to the bacterial second messenger c-di-GMP. The structures of human STING in the presence and absence of c-di-GMP show how recognition of c-di-GMP is achieved by dimeric STING, providing a basis for future studies investigating signal transduction mechanisms.

The crystal structures of human STING in the apo and c-di-GMP–bound states, supported by mutagenesis and biochemical data, reveal that c-di-GMP binds to preformed dimeric STING. c-di-GMP prolongs STING phosphorylation in vitro, which may contribute to downstream IFN signaling. These findings aid in understanding the innate immune response to bacterial infection.

STING is an ER-resident membrane protein that triggers cytokine production upon detection of the bacterial second messenger c-di-GMP. The structures of the cytosolic domain of STING and the complex it forms with c-di-GMP lay the groundwork for understanding STING function.

The process of pre-mRNA splicing involves connecting two exons while releasing the intron as a transient branched RNA, or as a lariat. Deep-sequencing analysis has enabled the first large-scale identification of branch points in human pre-mRNA transcripts in vivo, onto which the distribution of splicing factor binding was mapped.

AMP-activated protein kinase (AMPK) has a central role in sensing cellular metabolic levels. Crystal structures of the AMPK core in the presence of AMP or ATP suggest that the third nucleotide-binding site in the γ subunit is important for allosteric regulation of kinase activity.

Poly ADP-ribosylation regulates cellular processes such as genomic stability maintenance, transcription and cell death. The structure of a mammalian poly(ADP-ribose) glycohydrolase gives insight into the enzyme's endoglycosidase activity and provides a basis for the development of therapeutic inhibitors.

Primary microRNA cleavage by the Microprocessor complex comprising Drosha and DGCR8 needs to be specific yet efficient. Mathematical modeling complemented with experimental analysis now shows that autoregulatory feedback on DGCR8 expression is crucial for balancing the efficiency and specificity of Microprocessor activity.

Group II introns, which are self-splicing catalytic RNAs, catalyze splicing in two distinct steps. The crystal structure of a group II intron in the pre-catalytic state directly preceding the first splicing step reveals a sharp kink in the backbone that presents the scissile phosphate of the splice site to the active site.

Interleukin-1 (IL-1) cytokines are important mediators of the innate and adaptive immune response. The structure of IL-1β bound to its receptor (IL-IR) and receptor accessory protein (IL-1RAcP) provides an important model for how these cytokines initiate signaling.

SUMOylation targets HP1α to pericentric heterochromatin, but the enzyme responsible for removing the SUMO molecule from HP1α has not been determined. SENP7 is now identified as the factor that deconjugates SUMO, promoting retention of HP1α at these domains.

The crystal structure of the fusion protein from human metapneumovirus in complex with a potently neutralizing antibody reveals a novel antigenic site, which could be explored to develop vaccines against this and related paramyxoviruses.

Numerous methylated residues exist on histone tails, the functional significance of which remains unknown. New studies in budding yeast now identify monomethylation of histone H4 lysine residues 5, 8 and 12 as functionally important marks that regulate cell growth and stress responses and are catalyzed by the first known H4 methyltransferase in budding yeast, Set5.

Some bacterial pathogens can obtain iron from the human host by extracting it from transferrin via two bacterial surface proteins, TfbA and TfbB. Now the crystal structures of Neisseria meningitidis TfbB in its apo state and bound to human transferrin reveal how TfbB sequesters transferrin and initiates iron release.

Glutamate transporters couple the uptake of glutamate to the transport of cations. A new crystal structure of an archaeal trimeric glutamate transporter homolog, GltPh, captured in an intermediate conformation between the outward and inward facing states, provides insights into the transport mechanism.

Nuclear chromodomain-containing proteins read the epigenetic code by recognizing methylated lysine residues in histone tails. Structural analysis of the cytoplasmic chloroplast signal recognition particle subunit cpSRP34 in complex with the cpSRP54 subunit C-terminal tail comprising an arginine-rich motif reveals that a twinned aromatic cage reads two neighboring nonmethylated arginine residues and adapts chromodomains to a function outside the nucleus.