Editor's Note: Some of the articles described below are not yet available at the PNAS site but are scheduled to be posted this week.
Uppsala University researchers present findings from a retrovirus-focused analysis of the koala (Phascolarctos cinereus) genome. With the help of bioinformatics tools, the team analyzed sequenced koala genomes alongside a reference genome for the koala. In the process, they uncovered not only a koala retrovirus (KoRV) that is currently expanding in the koala genome, but also an earlier endogenous retrovirus (ERV) expansion that involved a linage known as phaCin-beta that resembled ERVs previously reported in squirrel monkeys. "[W]e present considerable evidence for recent phaCin-beta retrovirus activity in koala, resulting in an expansion of phaCin-beta ERVs in koala genomes," the authors conclude. "These findings generate a strong incentive for a new area of research into phaCin-beta retroviruses, and we anticipate future ERV-guided discovery of novel viruses along these lines in a variety of host species."
A University of Texas MD Anderson Cancer Center-led team proposes a tumor suppressor gene in another paper slated to appear in PNAS this week. Using CRISPR-based screening in vivo, the team searched for cell surface proteins with ties to tumor survival or spread with a single-guide RNA library targeting more than 1,100 proteins on the cell surface, focusing in on a suspected tumor suppressor gene called KIRREL that was subsequently linked to Hippo pathway signaling. While tumor growth was enhanced in the absence of the gene, the authors report, additional screens and follow-up analyses suggested KIRREL suppresses tumor activity through the Hippo pathway. The findings point to "a role of KIRREL in tumorigenesis via regulating the Hippo pathway," they write, "and further establish integrated CRISPR screening as an effective tool for defining the functions and the underlying mechanisms of genes involved in cancer development and other diseases."
Pennsylvania State University investigators track transfer RNA (tRNA) folding patterns and secondary structures across the Escherichia coli genome in vivo in response to heat stress using a workflow known as tRNA structure-seq — an approach that relies on ultra-processive reverse transcription, mutational profiling, and a structure probing chemical called dimethyl sulfate. "Our application of tRNA structure-seq yields insights into tRNA structure in living cells, revealing that it is not immutable but has dynamics, with partial unfolding of secondary and tertiary tRNA structure under heat stress that is correlated with a loss of tRNA abundance," the team writes, noting that "[g]iven that aberrant tRNA folding and modification cause severe human disease, tRNA structure-seq may have medical relevance."