Drosha and Pasha

No, this isn’t a Russian short story.

Lead authors postdoc alum Sebastian Kadener and Mol Cell Biol graduate student Joe Rodriguez and their coworkers used tiling arrays to look for targets of the enzyme Drosha in “Genome-wide identification of targets of the drosha–pasha/DGCR8 complex”, a paper recently published in the journal RNA. Drosha is a type III RNAse that is involved in the processing of  miRNAs. This paper demonstrates for first time that this enzyme is not only involved in miRNA processing, but can also process mRNAs.  Interestingly, the best example of an mRNA processed by Drosha is the mRNA that encodes another miRNA processing enzyme, the protein Pasha. As this is a partner of Drosha (the two proteins work together), the findings suggest that  there is a feedback loop that controls the abundance of the miRNA processing machinery and probably the abundance of miRNAs themselves.

Chloride channels and antiport mechanism

In a new paper in Journal of General Physiology, Brandeis postdoc Hyun-Ho Lim and Professor Christopher Miller examine the detailed mechanism by which a chloride transporter protein works. In particular, this protein does a rather crazy thing: it stoichiometrically swaps a proton on one side of the membrane for two Cl- ions on the other, and countertransports them across the membrane.  In this work, the authors identify a special glutamate residue on the cytoplasmic side of the protein that is responsible for picking up protons on that side in order to carry out this “antiport” mechanism.  (That glutamate is indicated by the spacefilled residue with red oxygen atoms in this depiction of the dimeric protein.)

Is my DNA fixed yet?

A broken chromosome (a double-strand DNA break) activates the DNA damage checkpoint to prevent cells from carrying out mitosis until the break has been repaired.  Repair of the break involves the modification and the removal of histone protein octamers from DNA around the break and these must be reestablished when repair is complete.  In a new paper in PNAS, Brandeis alumnus Jung-Ae Kim (Ph.D., Molecular and Cell Biology, 2008) and Professor James Haber show that when two of the major histone chaperone protein complexes (Asf1 and CAF-1) are deleted in yeast cells, their absence prevents cells from turning off the DNA damage checkpoint and hence cells stay permanently arrested.   These results suggest that cells specifically monitor the re-establishment of normal chromatin status after DNA repair.

Recent Grant Awards

Neuroscience Ph.D. candidate Melanie Gainey received an NRSA Fellowship from NINDS. Working in the Turrigiano lab, Melanie plans to study the role of the AMPA receptor subunit GluR2 in synaptic scaling in cultural neurons and in vivo using a conditional GluR2 knockout mouse.

Assistant Professor Suzanne Paradis received a Smith Family New Investigator Award from the Richard & Susan Smith Family Foundation. $300,000 in support over three years will support the lab’s efforts to study synapse development and specifically the role of the Sema4B protein in controlling synapse formation.

Professor Leslie Griffith received $1.1 million over 5 years from NIMH to study why sleep is required for effective memory formation. To understand this linkage at a cellular and molecular level, the Griffith lab is defining the circuits that regulate sleep in Drosophila and how these circuits affect memory formation.

Professor Larry Wangh received $1.38 million over the next year from Smiths Detection to continue research and invention of LATE-PCR et al., platform technologies for highly informative detection and diagnosis of nucleic acids in a single tube.  There are ongoing projects looking at applications to cancer, prenatal genetics, and several infectious diseases in people and animals.

Channel proteins that aren't

What happens when you take an ion channel and remove all the parts that conduct ions? The answer might be surprising.

The Drosophila ether-à-go-go gene codes for a potassium channel involved in olfaction, learning, and locomotion. It is not solely a potassium channel, however. In a recent paper in Mol. Cell. Neurosci., Brandeis postdoc alum Xiu Xia Sun and Neuroscience grad student Lynn Bostrom from the Griffith lab show that an alternatively spliced form, Eag80, contains no channel domains and localizes to the nucleus. They further show that Eag80 can act to activate signal transduction pathways. This splicing can be stimulated by calcium and protein kinases, suggesting that this splice form may have a significant role in regulating neuronal function.

Sigma factors

In a new study appearing in PNAS this week, Brandeis Molecular and Cell Biology graduate student Houra Merrikh and co-workers from the Lovett lab identified the E.coli gene iraD as a regulator of the response to oxidative DNA damage in exponentially growing bacteria. Interestingly, the mechanism seems to involve the alternative RNA polymerase sigma factor RpoS, previously characterized as a regulator of expression during the “stationary phase”. Merrikh et al. argue that this response works in parallel with the previously characterized SOS response in protecting growing bacteria from DNA damage.

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