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Here, the authors review the fast-moving field of gene expression regulation by microRNAs. They describe how microRNAs influence many stages of innate and adaptive immune responses and how they might precipitate cancer and autoimmune disease if dysregulated.

This Review details the key roles of microRNAs (miRNAs) in regulating immune cell development and function. The authors describe how miRNAs govern cell fate decisions during haematopoiesis and discuss how aberrant miRNA expression can lead to pathologies such as autoimmunity and cancer.

The discovery of modular protein- and lipid-binding domains was a crucial turning point in our understanding of the logic and evolution of cell signalling mechanisms. The late, great Tony Pawson was instrumental in their discovery.

Diffuse large B-cell lymphoma (DLBCL) is curable in advanced stages, but up to one-third of patients will ultimately fail to respond to initial therapy. As we have now entered the molecular era of defining DLBCL, the goal is to pinpoint driver mutations and pathway addictions within distinct molecular subsets of DLBCL. This Review describes the current molecular understanding of DLBCL and discusses promising targeted approaches for each subtype.

Mitochondria are emerging as important players in innate immunity: they act as signalling platforms for antiviral molecules, produce reactive oxygen species that influence both antiviral and antibacterial immune responses and are a source of factors that initiate sterile inflammation.

The B cell receptor (BCR) activates numerous survival and proliferation pathways, and can signal in an antigen-dependent or antigen-independent (tonic) fashion. Here, Young and Staudt discuss the signalling cascades involved, examine recent evidence for a role of BCR signalling in different subtypes of B cell lymphomas and provide an overview of pipeline candidates that target components of the BCR signalling cascade.

Retroviruses, which encode fewer than ten genes, need to interact with cellular proteins for virtually all aspects of their replication cycle. In this Review, Stephen Goff describes how host factors and cellular pathways are exploited at each stage of the retrovirus lifecycle. Throughout, comparisons are drawn between HIV and other retroviruses.

Knipe and Cliffe review the mechanisms that underlie the switch from a lytic to a latent infection in the widespread pathogen herpes simplex virus (HSV). They propose a new model in which an epigenetic switch determines whether a lytic or a latent infection occurs and discuss viral functions that might regulate chromatin assembly on the HSV genome and effect this epigenetic switch.

This Review provides a very accessible summary of the mechanisms of V(D)J recombination, including the role of the chromatin architecture and histone modifications in determining accessibility for RAG (recombination activating gene) protein binding. The authors discuss potential models for RAG specificity and summarize the major outstanding questions in this field.

Somatic hypermutation (SHM) introduces mutations in the variable region of immunoglobulin genes, to generate high-affinity B-cell antigen receptors. But, as discussed in this Review, how SHM is targeted to immunoglobulin genes is a subject of intense research and debate.

RNA viruses have extremely high mutation rates, which are crucial for the ability of these viruses to adapt but can also lead to population extinction. Here, Andino and colleagues describe the mechanisms that RNA viruses use to cope with the high mutational load and discuss the impact of mutational robustness on population dynamics, pathogenicity and antiviral therapies.

The terminal differentiation of antibody-secreting cells is controlled by a network of antagonistic transcription factors and, although it is highly complex, this process can be explained by a simple probabilistic differentiation process.

MicroRNAs are exciting new regulators of genes involved in cell growth and development. Regulatory roles for microRNAs have been identified in plants and animals, but these tiny regulators have not been found in bacteria or fungi. Here, Sarnow and colleagues discuss the fascinating roles of both virus- and host-cell-encoded microRNAs in virus lifestyles.

Although inhibition of tyrosine kinases has revolutionized cancer therapy, some of the inhibitors used have now been associated with cardiotoxicity. How does inhibition of cancer-relevant signalling pathways affect heart cells, and how can these effects be minimized?

Activation of nuclear factor-κB (NF-κB) is crucial for initiating inflammatory responses. In this Review, Sankar Ghosh and Matthew Hayden discuss the roles of several newly identified regulators of the NF-κB pathway, as well as some old factors that have been assigned new functions.

Mutant p53 proteins not only lose their tumour suppressive ability, but also gain new properties that promote tumorigenesis. What are these properties and what are the clinical implications?

The ways in which an RNA molecule folds to form structures can be crucial to its function, and so methods for studying RNA structures make an important contribution to understanding transcriptomes. Experimental approaches in this field are being advanced by coupling them to high-throughput sequencing.