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This Week in PNAS: Sep 21, 2010

In the PNAS Early Edition this week, investigators in Japan show that miR-33, encoded by an intron of Srebp2, regulates HDL cholesterol in vivo. Using miR-33-deficient mice, the team found that "miR-33 repressed the expression of ATP-binding cassette transporter A1 protein, a key regulator of HDL synthesis, by mediating cholesterol efflux from cells to apolipoprotein A-I," they write. They also found that mice lacking miR-33 show a "marked increased in ABCA1 levels and higher apoA-I–dependent cholesterol efflux" than wild-type mice.

Researchers at the University of Texas MD Anderson Cancer Center report that portions of the "INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway." Specifically, Yingjun Jiang et al. show that the deletion of INO80 and ARP5 "significantly hampered cellular removal of UV-induced photo lesions but had no significant impact on the transcription of NER factors" in mammalian genetic models. The protein products of these genes are recruited to UV-damaged DNA "in an NER-incision-independent fashion," the authors write.

Nabil Elrouby and George Coupland at the Max Planck Institute for Plant Breeding Research describe their proteome-wide screens for small ubiquitin-like modifier substrates in Arabidopsis, which they discovered are "involved in a wide range of plant processes, many of which were not previously known to involve SUMOylation." Overall, Elrouby and Coupland identified 238 potential SUMO substrates that interacted with "SUMO-conjugating enzyme and/or SUMO protease (ESD4) in the yeast two-hybrid system," which they then interrogated in an E. coli system. "More than 92 percent of the proteins tested were SUMOylated in this assay by at least one SUMO isoform," the duo writes.

In another PNAS paper published online in advance, the National University of Ireland's James Cotton and James McInerney at Queen Mary University of London suggest that "eukaryotic genes of archaebacterial origin are more important than the more numerous eubacterial genes, irrespective of function." Archaebacterium-derived genes, Cotton and McInerney write, are more highly expressed, more likely to be essential to viability, and "more highly connected and more central in the yeast protein interaction network … irrespective of whether the genes have an informational or operational function."

The Scan

New Study Investigates Genomics of Fanconi Anemia Repair Pathway in Cancer

A Rockefeller University team reports in Nature that FA repair deficiency leads to structural variants that can contribute to genomic instability.

Study Reveals Potential Sex-Specific Role for Noncoding RNA in Depression

A long, noncoding RNA called FEDORA appears to be a sex-specific regulator of major depressive disorder, affecting more women, researchers report in Science Advances.

New mRNA Vaccines Offer Hope for Fighting Malaria

A George Washington University-led team has developed mRNA vaccines for malaria that appear to provide protection in mice, as they report in NPJ Vaccines.

Unique Germline Variants Found Among Black Prostate Cancer Patients

Through an exome sequencing study appearing in JCO Precision Oncology, researchers have found unique pathogenic or likely pathogenic variants within a cohort of Black prostate cancer patients.