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This Week in Cell: Jan 2, 2013

The University of Massachusetts Medical School's Craig Mello and his colleagues report in Cell that they have uncovered a new type of piwi-interacting RNA in Caenorhabditis elegans. Using a new enzymatic method for 5' anchored RNA profiling called CapSeq, the researchers found a number of candidate transcription start sites for piRNA precursors. However, the researchers say that using that they could not identify the vast majority of piRNA loci. Instead, they combined the CapSeq approach with CAP-TAG to identify polymerase-binding sites, noting that many piRNA precursors are capped, small RNAs that are about 26 nucleotides in length. "The findings described here add to the amazing variety of piRNA biogenesis mechanisms and identify a second type of piRNA that nearly doubles the number of piRNA species available for genome defense in C. elegans," Mello and his colleagues add. "The finding that small RNAs associated with TS sites are processed and loaded onto an Argonaute also raises an intriguing possibility that Argonaute-small RNA pathways might regulate promoter activity directly."

Also in Cell, Hans Clevers from the Hubrecht Institute and the University Medical Center Utrecht in The Netherlands and his colleagues present their work implicating the transcription factor TCF4 in activating metabolic genes. TCF4 is a diabetes risk gene and a Wnt effector. Working in mouse knock-out models, the researchers found that not having TCF4 in liver beta cells does not affect the function of those cells while changing TCF4 levels in the liver itself does affect metabolism. Using ChIP-seq as well as gene expression profiling, the researchers found a "TCF4-controlled metabolic gene program that is acutely activated in the postnatal liver."

Finally, the University of California, San Diego's Jonathan Sebat and his colleagues report that genes associated with autism-spectrum disorders are often located in regions of the human genome that are hyper-mutable. The researchers sequenced the whole genomes of 10 monozygotic twins, concordant for an autism-spectrum disorder, and their parents. Using data gleaned from the twins' genomes, the researchers noted that regions of mutability are spaced nonrandomly throughout the genome, and they then developed a model to predict a genome region's mutability. "Wide variation in regional mutation rates can be explained by intrinsic characteristics of the genome," Sebat and his colleagues add. "Furthermore, we find significant evidence that genes impacted by [de novo mutations] in twins are associated with autism in independent cohorts."

Our sister publication GenomeWeb Daily News has more on this paper here.

The Scan

Transcriptomic, Epigenetic Study Appears to Explain Anti-Viral Effects of TB Vaccine

Researchers report in Science Advances on an interferon signature and long-term shifts in monocyte cell DNA methylation in Bacille Calmette-Guérin-vaccinated infant samples.

DNA Storage Method Taps Into Gene Editing Technology

With a dual-plasmid system informed by gene editing, researchers re-wrote DNA sequences in E. coli to store Charles Dickens prose over hundreds of generations, as they recount in Science Advances.

Researchers Model Microbiome Dynamics in Effort to Understand Chronic Human Conditions

Investigators demonstrate in PLOS Computational Biology a computational method for following microbiome dynamics in the absence of longitudinally collected samples.

New Study Highlights Role of Genetics in ADHD

Researchers report in Nature Genetics on differences in genetic architecture between ADHD affecting children versus ADHD that persists into adulthood or is diagnosed in adults.