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This Week in Nature: Jun 17, 2010

In an advance, online publication of Nature this week, researchers at the University of Wisconsin-Madison report that "small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription." They show that "gene nuclear RNAi defective-2 (nrde-2) encodes an evolutionarily conserved protein that is required for siRNA-mediated silencing in nuclei." The team suggests that their results "demonstrate that metazoan siRNAs can silence nuclear-localized RNAs co-transcriptionally."

In a letter published in this week's Nature, investigators at the Institut de Génétique et de Biologie Moléculaire et Cellulaire and their colleagues suggest that transcription factor IIA and Rap1 "cooperate to commit transcription factor IID for transcription initiation." Using cry-electron microscopy, the team was able to determine the architecture of nucleoprotein complexes — made of TFs IIA and IID and the transcriptional activator Rap1 — and yeast enhancer-promoter DNA. "A large Rap1-dependent DNA loop forms between the activator-binding site and the proximal promoter region," and "this loop is topologically locked by a TFIIA–Rap1 protein bridge that folds over the DNA," the authors show.

Nazneen Rahman at the Institute of Cancer Research in the UK and her collaborators present genome-wide association study-based evidence that a variant near DMRT1, TERT, and ATF71P are associated with testicular germ cell cancer in Nature Genetics this week. By genotyping 979 affected individuals and nearly 5,000 controls, and replicating their associations in 664 additional cases and nearly 3,500 extra controls, the team "identified two independent signals within the TERT-CLPTM1L locus on chromosome 5," and also elucidated hits at ATF71P, a regulator of TERT expression, and DMRT1, "which has been linked to teratoma susceptibility in mice," they write.

Inna Povolotskaya and Fyodor Kondrashov at the Centre for Genomic Regulation in Barcelona opine that "the need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions" in a Nature letter published this week. The authors "explore the limits of protein evolution using sequence divergence data" and "formulate a computational approach to study the rate of divergence." They suggest that ancient proteins are still diverging from one another, "indicating an ongoing expansion of the protein sequence universe."

The Scan

Expanded Genetic Testing Uncovers Hereditary Cancer Risk in Significant Subset of Cancer Patients

In Genome Medicine, researchers found pathogenic or likely pathogenic hereditary cancer risk variants in close to 17 percent of the 17,523 patients profiled with expanded germline genetic testing.

Mitochondrial Replacement Therapy Embryos Appear Largely Normal in Single-Cell 'Omics Analyses

Embryos produced with spindle transfer-based mitochondrial replacement had delayed demethylation, but typical aneuploidy and transcriptome features in a PLOS Biology study.

Cancer Patients Report Quality of Life Benefits for Immune Checkpoint Inhibitors

Immune checkpoint inhibitor immunotherapy was linked in JAMA Network Open to enhanced quality of life compared to other treatment types in cancer patients.

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.