In the PNAS Early Edition this week, investigators at the DDC Clinic for Special Needs Children in Middleton, Ohio, "describe an autosomal recessive condition characterized with cerebral vasculopathy and early onset of stroke in 14 individuals in Old Order Amish." Using candidate gene sequencing, they found that the condition is caused by a homozygous mutation in the SAMHD1 gene. "The mutation appeared at the splice-acceptor site of intron 12, resulted in the skipping of exon 13, and gave rise to an aberrant protein with in-frame deletion of 31 amino acids," the authors write, adding that though the function of the SAMHD1 protein is as yet unclear, "the inflammatory vasculopathies of the brain found in the patients with SAMHD1 mutation indicate its important roles in immunoregulation and cerebral vascular hemeostasis."
Hong-Ru Lin and Don Ganem at the University of California, San Francisco, this week show that a naturally occurring viral microRNA target "is situated … in the coding region of one transcript and in the 3'-UTR of an overlapping mRNA," such that it "allows insight into the role of translation in governing miRNA target accessibility." In particular, the team found that while miRNAs "can exert regulatory effects on targets within coding regions," these effects are reduced by translation and therefore "likely account for the observed selection of target sites."
The University of Chicago's Yan Yuan Tsenga and Wen-Hsiung Li present an approach to predict "binding site residues of a protein from its primary sequence," based on their clustering in evolutionarily conserved functional pockets. "To take advantage of these evolutionary and structural principles, we constructed a database of [about] 50,000 templates — called the pocket-containing segment database," the authors write. They add that using their template-matching technique, they could probabilistically assign the "binding likelihood of each matched residue in the query sequence" with 70 percent precision at 60 percent sensitivity.
A team of researchers at Johns Hopkins shows that "high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy." By reducing Mps1 expression in cultured human breast cancer cells by RNAi, the team observed aberrant mitosis and the induction of apoptosis, among other events.