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.

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.

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.

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.

At each ovulation cycle, the single-layer epithelia that encapsulate mammalian ovaries undergo rupture and rapid repair. Recent studies have identified stem cell pools that ensure ovarian epithelial homeostasis, thus providing insights into the regulation of stem cell function and the contribution of stem cells to ovarian tumorigenesis.

The unique physical and chemical properties of microfluidic devices have underpinned notable recent advances in molecular cell biology research and will facilitate a new era of biological enquiry of increased precision.

DNA methylation and H3K9 methylation are typically associated with gene silencing. Genetic, genomic, structural and biochemical data reveal functional connections between these two epigenetic marks. They also highlight how specialized protein domains that recognize the marks are essential for their establishment and maintenance at appropriate genomic loci.

Measurement of protein binding to a large number of RNA variants reveals binding patterns and helps to quantify binding specificities, which enables the development of RNA–protein interaction models. Such models are changing the binary view of RNA binding by proteins as either specific or nonspecific.

The recent discovery of the genes encoding components of the mitochondrial calcium uniporter paves the way for further study of its mechanism of action and its relevance to physiological and pathological processes.

Aneuploidy, which results from chromosome mis-segregation, is a hallmark of cancer, but it can also inhibit tumorigenesis. Recent studies on the short- and long-term consequences of aneuploidy, which are caused by gene-specific effects and a stereotypic aneuploidy stress response, provide insights into this contradictory role in tumorigenesis.