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This Week in PNAS: Jan 11, 2011

In the PNAS Early Edition this week, researchers at Michigan State University and their colleagues show that Pack-Mutator-like transposable elements "specifically acquire GC-rich fragments and preferentially insert into the 5' end of genes" in Arabidopsis, which they say "may influence the conformation of chromatin, the expression level of genes, as well as the recombination rate." These Pack-Mutator-like transposable elements — or Pack-MULEs — "form independent, GC-rich transcripts with a negative GC gradient" or themselves "evolve into additional exons at the 5′ end of existing genes, thus altering the GC content in those regions," the authors write.

Investigators in Italy and Brazil this week show that the cardiac-specific knockout of Hcn4, the pacemaker channel gene, causes fatal deep bradycardia and heart block ablation in mice. The team's immunofluorescence and Western blot analyses corroborated its functional findings as they both "showed reduced expression of HCN4 protein in [sinoatrial node] tissue and cells," the authors write. As a result of its study, the team concluded that "cardiac HCN4 channels are essential for normal heart impulse generation and conduction in adult mice and support the notion that dysfunctional HCN4 channels can be a direct cause of rhythm disorders."

The Stanford University School of Medicine's Selena Sagan and her colleagues report in this week's PNAS that miRNA-122 forms an "unconventional microRNA-target RNA complex," that occludes the 5' terminal nucleotides of the hepatitis C virus genome." This complex "protects the 5' terminal viral sequences from nucleolytic degradation or from inducing innate immune responses to the RNA terminus," Sagan et al. show.

And investigators at the Australian Research Council Centre of Excellence in Plant Energy Biology — along with their colleague at the University of Western Australia — report that pentatricopeptide repeat protein-encoding genes related to the restorer-like genes required for male gametophyte development are expressed extensively across plant genomic sequence. The Australian team suggests that, because of the chromosomal clustering and "notably high rates of non-synonymous to synonymous substitutions" they've observed, these genes have been subjected to diversifying selection. "The selection patterns on [fertility restorer]-like genes reveal a molecular 'arms-race' between the nuclear and mitochondrial genomes that has persisted throughout most of the evolutionary history of angiosperms," the authors propose in PNAS.

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.