Alexandra A. Mushegian

Autophagy and vitamin D

Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression. Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression.

Sources of variation: Animal microbiota

The diverse effects of microbiota on animal physiology contribute to experimental variability. The diverse effects of microbiota on animal physiology contribute to experimental variability.

A ribosomal strategy for magnesium deficiency

Under low-magnesium stress, bacteria suppress ribosome synthesis. Because most ribosomes in a cell are typically actively translating at maximum capacity, the overall rate of protein synthesis is often determined by the rate of ribosome synthesis. Pontes et al. found that under stress due to low concentrations of magnesium ions, bacterial cells maintained minimal protein synthesis by suppressing ribosome synthesis and conserving magnesium for ribosome maintenance. Divalent magnesium ions (Mg2+) are essential for several aspects of protein synthesis, including neutralizing the charge on ribosomal RNA (rRNA) to allow it to correctly fold; removing Mg2+ causes ribosomes to disassemble. In Salmonella enterica growing in culture media containing low Mg2+, transcription of ribosomal RNA (the rate-limiting step in ribosome synthesis) was 10-fold lower than under high Mg2+ conditions, whereas transcription of a control gene was unaffected. rRNA transcription was suppressed by proteins involved in Mg2+ homeostasis. mgtA and mgtB encode Mg2+ transporters and mgtC encodes an inhibitor of F1FO ATP synthase that increases the amount of cytosolic Mg2+ by inhibiting the production of ATP, which has a high affinity for Mg2+. Mutations in mgtC alone or in both mgtA and mgtB resulted in higher rRNA transcription under low-magnesium conditions. Expressing ATPase in these mutants reduced rRNA expression to a value similar to that in wild-type cells, suggesting that the accumulation of ATP in cells lacking these magnesium regulators drove rRNA transcription. Cells lacking phoP—which encodes a transcription factor that regulates mgtA, mgtB, and mgtC—also had increased rRNA transcription under low-magnesium conditions. However, phoP mutant cells grow more slowly than wild-type cells, suggesting that under magnesium starvation, growth rate is not linked to ribosome synthesis. In mgtC mutant and mgtA/mgtB double-mutant cells grown under low Mg2+, the 30S and 50S ribosomal subunits accumulated but did not assemble into functional 70S ribosomes, as determined by sucrose gradient fractionation of polysomes. Wild-type bacteria and mgtC or mgtA/mgtB mutant cells rescued by expression of the respective genes on plasmids had normally assembled 70S ribosomes. Thus, in response to low Mg2+, maintenance of intracellular Mg2+ by phoP-regulated proteins reduced overall rRNA transcription but was required for ribosome assembly, creating a new stress-adapted phenotype. M. H. Pontes, J. Yeom, E. A. Groisman, Reducing ribosome biosynthesis promotes translation during low Mg2+ stress. Mol. Cell 64, 480–492 (2016). [PubMed]

When silencing mRNA, position matters

The mechanism of posttranscriptional silencing by an RNA-binding protein depends on the position of the protein-binding sequence in the mRNA. The mechanism of posttranscriptional silencing by an RNA-binding protein depends on the position of the protein-binding sequence in the mRNA.

Harnessing innate immunity to fight neurodegeneration

TRIM21 prevents antibody-bound tau proteins from aggregating in cells. TRIM21 prevents antibody-bound tau proteins from aggregating in cells.

Stress signals in plants

Selective autophagy mediates the cross-talk between plant growth and stress signaling pathways. Selective autophagy mediates the cross-talk between plant growth and stress signaling pathways.

Microbiome-dependent recombination shapes the host antibody repertoire.

Secreted IgD concentration depends on the presence of microbiota. Secreted IgD concentration depends on the presence of microbiota.

An insulin-like message from mother

Nematodes experiencing osmotic stress signal to the germ-line to prepare their offspring. Nematodes experiencing osmotic stress signal to the germ-line to prepare their offspring.

Recovering rRNA processing after heat shock

NF-κB repressing factor controls localization and activation of an rRNA processing protein in heat stress response. NF-κB repressing factor controls localization and activation of an rRNA processing protein in heat stress response.

Polyglutamine makes the switch

In worms, a regulator of noncoding RNA directly catalyzes formation of toxic protein aggregates in the presence of polyglutamine. In worms, a regulator of noncoding RNA directly catalyzes formation of toxic protein aggregates in the presence of polyglutamine.