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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

Interfering With Invasive Mussels

The Chicago Tribune reports that researchers are studying whether RNA interference- or CRISPR-based approaches can combat invasive freshwater mussels.

Participation Analysis

A new study finds that women tend to participate less at scientific meetings but that some changes can lead to increased involvement, the Guardian reports.

Right Whales' Decline

A research study plans to use genetic analysis to gain insight into population decline among North American right whales, according to CBC.

Science Papers Tie Rare Mutations to Short Stature, Immunodeficiency; Present Single-Cell Transcriptomics Map

In Science this week: pair of mutations in one gene uncovered in brothers with short stature and immunodeficiency, and more.