Reviews & Analysis

The CRISPR–Cas9 system is a powerful, sequence-specific tool that was initially developed for gene and genome editing. The recent adoption of nuclease-deactivated Cas9 (dCas9) has enabled expansion of the use of the system to multiplexed and inducible transcription regulation, genome-wide screens and cell fate engineering.

In addition to its known roles in nonsense-mediated mRNA decay, recent findings show that the exon junction complex (EJC) participates in diverse mRNA maturation processes, including splicing, transport and translation. This multi-functionality is reflected by an increasing number of EJC-related disorders being discovered.

ADAR enzymes convert adenosine to inosine (A-to-I editing) at numerous double-stranded Alu repeats in human transcripts, thereby affecting many cellular processes. Primary microRNAs (miRNAs) are also edited, and ADAR1 directly interacts with Dicer, resulting in the modulation of miRNA expression and activity and of downstream gene expression programmes during embryogenesis.

Endoplasmic reticulum (ER) is typically associated with protein biogenesis. However, recent studies suggest that it additionally synchronizes and regulates a plethora of intracellular events owing to its ability to form tight membrane associations, so-called membrane contact sites (MCSs), with other organelles.

Most eukaryotic centromeres are defined epigenetically and require nucleosomes containing the histone H3 variant centromere protein A (CENP-A). We are now gaining insight into the mechanisms that regulate CENP-A deposition and positioning to specify and propagate centromeres during cell division, and into the function of centromeres in recruiting kinetochores to connect chromosomes to spindle microtubules.

Recent studies inArabidopsis thalianahave identified interconnected signalling networks that regulate plant vascular development. These findings have increased our understanding of vascular development from early cell specification during embryogenesis to the latest stages of differentiation of the phloem and xylem.

Catenins are typically considered to function at cell–cell junctions. However, it has recently become evident that multiple catenins can enter the nucleus and regulate gene expression. Thus, catenins might form complex networks, coupling membrane-associated signalling with transcriptional events.

Microtubule plus ends and minus ends accumulate specific sets of proteins that can regulate microtubule dynamics, connect microtubules to cellular structures and recruit signalling molecules that collectively control cellular behaviour. Our knowledge of the factors that associate with microtubule ends, and the mechanisms through which they do this, has strongly increased in recent years.

Plant genomes encode diverse small RNAs, such as microRNAs, secondary siRNAs, heterochromatic siRNAs and various RNA-dependent RNA polymerases, DICER proteins and ARGONAUTE proteins. Together, these constitute several genetic and epigenetic silencing pathways with diverse cellular and developmental functions, in processes including reproductive transitions, genomic imprinting and paramutation.

Recent studies have changed our understanding of the prevalence and biological significance of DNAN⁶-adenine methylation (6mA) in eukaryotes. This modification is involved in regulating transcription, transposable elements and epigenetic inheritance, and thus can be considered to be a eukaryotic epigenetic mark.

Lipids tailor membrane identities and function as molecular hubs in all cellular processes. The development of pioneering technologies, including affinity-purification lipidomics and the liposome microarray-based assay (LiMA), will enable researchers to decipher protein–lipid interactions and enhance our understanding of how lipids modulate protein function and structure.

Glucose from excess dietary carbohydrate is converted to fatty acids in the liver throughde novolipogenesis. Lipogenic genes have common features in their promoters and are coordinately regulated at the transcriptional level. Recent insights have been gained into the signalling pathways that regulate key transcription factors such as USFs, SREBP1C, LXRs and ChREBP.

Ribosome profiling has the power to interrogate —in vivoand on a global scale — what is being translated, how this translation is regulated and where in the cell the translation of specific sets of proteins occurs.

Membrane and soluble secretory proteins are glycosylated in the endoplasmic reticulum. The addition ofN-linked glycans is important for protein folding and quality control, whereas O-linked mannoses have distinct functions in protein quality control. Recent studies have revealed the complexity of these glycan-directed modifications in protein biogenesis and degradation.

Recent findings have demonstrated that Polycomb repressive complexes (PRCs) control gene expression through their co-recruitment to specific CpG island elements with transcription factors and non-coding RNAs. Moreover, they revealed that the interplay between PRC1 and PRC2 to achieve transcriptional repression is more intricate than was previously thought.

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.

Nonsense-mediated mRNA decay (NMD) degrades mRNAs with abnormally positioned translation termination codons. It is now becoming apparent that NMD targets mRNAs to enable mammalian cells to adjust their transcriptomes and their proteomes to changing physiological conditions and during diverse cellular processes.

The chromatin-based epigenetic changes that occur during ageing and the role of chromatin modifiers in lifespan have recently been highlighted. The importance of epigenome remodelling by environmental stimuli for transcriptional and genomic stability is emerging, and such remodelling could provide new targets to counter ageing or age-related diseases.

Centrosomes are important microtubule organizers. As many proteins are concentrated at centrosomes, including cell cycle and signalling regulators, centrosomes are also likely to coordinate important cell decisions. Recent findings have shed light on the functions of centrosomes in animal cells and on the mechanisms of centrosome assembly and maturation during mitosis.

Recent findings revealed the extent to which mitochondrial translation and other cellular processes are mutually controlled. Mitochondrial translation is coordinated with the assembly of respiratory chain complexes and is positively regulated by microRNAs imported from the cytoplasm. In turn, mitochondrial translation stress activates retrograde signalling pathways that suppress cell proliferation.