Research Highlights in 2017

Totipotency is the ability of a single cell to form an entire embryo, including extraembryonic tissues, an ability we have yet to recapitalize, in vitro. In a recent paper published in Science, Choi et al. showed that pluripotent stem cells lacking microRNA miR-34a, have an expanded cell fate potential allowing differentiation into not only embryonic but also extraembryonic lineages.

Targeted proteolysis plays an important role in the execution and regulation of many cellular events. Two recent papers in Science identify novel roles for proteasome-mediated proteolysis in homologous chromosome pairing, recombination, and segregation during meiosis.

The molecular mechanisms governing self-renewal and differentiation of the mammary epithelium are incompletely defined; a better understanding of the events implicated in the specification and expansion of luminal progenitors is of particular importance as many breast cancers originate from their transformation. Britschgi et al. found that, in addition to phosphorylating and inactivating YAP, LATS functions as a scaffold to facilitate estrogen receptor-α ubiquitylation by the E3 ligase CRL4^DCAF1 and consequently suppresses luminal progenitor specification and expansion.

In a recent Nature paper, Heintz et al. identify a splicing factor (SFA-1) that is crucial for the longevity conferred by dietary restriction and the TORC1 pathway modulation in C. elegans.

Although energy-dependent protein destruction by the proteasome has been known for over 30 years, how this intricate molecular machine uses ATP to power protein degradation has remained very poorly understood. In a recently published paper, Ding et al. present a snapshot of the proteasome mid-catalysis, yielding new and unexpected insights into the catalytic mechanism of this ATP-powered multisubunit machine.

In bacteria and archaea, CRISPR-Cas adaptive immune systems utilize RNA-guided endonucleases to defend against invasion by foreign nucleic acids of bacteriophage, virus and plasmid origin. In a recent paper published in Nature, Burstein et al. identified the first Cas9 protein in uncultivated archaea and two novel CRISPR-CasX and CRISPR-CasY systems in uncultivated bacteria by capitalizing on analysis of terabase-scale metagenomic datasets from natural uncultivated organisms.

Mitophagy, the selective autophagic elimination of mitochondria, is a conserved cellular process critical for maintaining normal cellular physiology, and defects in this process are associated with certain pathophysiologies. In a recently published paper, Wei et al. describe their discovery of a hitherto unexplored mechanism of marking mitochondria for degradation.

An ability to convert between pancreatic islet cell types may provide a new approach to replace insulin-secreting β cells destroyed by autoimmune attack in Type 1 diabetes. Two papers, which have recently appeared in Cell, describe how this might be achieved.

EGF, a well-studied mitogen for cancer cells, is revealed to induce an E3 ubiquitin ligase adaptor SPSB1, which recruits the Elongin B/C-Collin complex to trigger ubiquitylation of the negative splicing regulator hnRNP A1. This event is synergized with EGF-activated SR proteins to alter alternative splicing of a key small GTPase Rac1 to enhance cell migration, highlighting converging EGF signals on both negative and positive splicing regulators to jointly promote a key cancer pathway.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated genes (cas) are essential components of an adaptive immune system that protects bacteria and archaea from viral infection. Now a recent paper published in Cell Research suggests that the Type I-F immune system in Pseudomonas aeruginosa may also be involved in post-transcriptional regulation of virulence.

One of the key questions regarding macroautophagy/autophagy is the mechanism through which the transmembrane protein ATG9 functions in delivering membrane to the expanding phagophore, the sequestering compartment that matures into an autophagosome. In a recent study, Zhou et al. identified a novel mechanism that regulates ATG9 trafficking from the plasma membrane and trans-Golgi network, which involves two conserved sorting signals required for ATG9 interaction with the AP1/2 adaptor complex and phosphorylation of ATG9 at Tyr8 by SRC kinase and at Ser14 by ULK1 for proper function during basal and starvation-induced autophagy.