Articles in 2014

A new study identifies the splicing factor SRSF6 as a proto-oncogene frequently overexpressed in human skin cancer. SRSF6-overexpressing mice develop skin hyperplasia and aberrant alternative splicing, with SRSF6 binding to alternative exons of the pre-mRNA of the extracellular-matrix protein tenascin C, thus promoting expression of isoforms characteristic of invasive and metastatic cancer.

Cancer cells often exhibit hyperactive signaling pathways. A new study now shows that Plcγ1 competes with Grb2 for binding to the fibroblast growth factor receptor 2 (FGFR2) in nonstimulated cells. Reduction in Grb2 expression results in increased Plcγ1 activity and cell motility, thus providing a molecular basis for the observation that reduced Grb2 expression correlates with metastatic potential.

The voltage-sensing domain (VSD) of voltage-gated ion channels transitions from a resting to an activated conformation upon membrane polarization. EPR spectroscopy analysis has now determined the position of the KvAP VSD in a resting conformation, revealing a new ‘tilt-shift’ model for transitioning between resting and activated states.

Transcription termination correlates with the loss of Tyr1 phosphorylation from the C-terminal domain (CTD) of Rpb1, an event thought to be necessary for the recruitment of termination factors. The phosphatase Glc7, an integral component of the cleavage-and-polyadenylation factor (CPF), is now shown to dephosphorylate Tyr1 and to contribute to termination in vivo.

Autorepression of PER-encoding genes underlies the periodic fluctuations in expression that drive the circadian clock. New work shows that histone deacetylase and histone methyltransferase activities are sequentially recruited to promoters of PER-encoding genes by separate PER protein–containing complexes and repress transcription via histone H3K9 modifications at those targets.

Some cancer cells lacking telomerase activity extend their telomeres via an alternative, recombination-based mechanism, termed ALT. A new study shows that depletion of histone chaperone ASF1 can induce ALT in both primary and cancer cells, suggesting that the ALT pathway may be triggered by changes in chromatin state.

Functional analyses of the ABC-F protein YjjK (EttA) suggest that it acts as a sensor of cellular energy and controls entry into the translational elongation cycle. Using cryo-EM and single-molecule FRET, EttA is shown to bind the ribosomal E site and engage both the L1 stalk and P-site tRNA to restrain ribosomal dynamics.

Although ABC-F proteins represent a ubiquitously distributed type of ATP-binding cassette (ABC) family member across phyla, their biological functions remain poorly characterized. A new study now shows that the bacterial ABC-F protein YjjK (EttA) gates ribosome entry into the translational cycle in an energy-dependent manner.