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This Week in Nucleic Acids Research: Mar 23, 2011

Published in advance in Nucleic Acids Research this week, the University of Texas Southwestern Medical Center's Scott Younger and David Corey present their computational method to identify potential miRNA target sites within gene promoters. The researchers tested 10 candidate miRNAs, which are predicted to target the human progesterone receptor gene promoter, for their ability to modulate gene expression, and found evidence of chromatin-level silencing by an RNA mimic. "While additional investigations of endogenous miRNA function will be necessary, these observations suggest that recognition of gene promoters by miRNAs may be a natural and general mechanism for regulating gene transcription," the authors write.

Also published in advance in Nucleic Acids Research this week, a team in Australia says global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage. The researchers performed parallel analysis of RNA ends and found that numerous mRNAs are potentially targeted for cleavage by endogenous miRNAs. "[The] analysis also identified many examples of adenylated small non-coding RNAs, including microRNAs, tRNA processing intermediates and various other small RNAs, consistent with adenylation being part of a widespread proof-reading and/or degradation pathway for small RNAs," the authors write.

A team at Duke University Medical Center has identified a novel retrotransposed imprinted locus at human 6p25. Using quantitative DNA methylation analysis, the researchers found a differentially methylated region at the 5′-end of FAM50B at 6p25.2 and determined that "sense transcripts originating from the FAM50B locus are expressed from the paternal allele in all human tissues investigated except for ovary, in which expression is biallelic." These findings suggest that FAM50B originated in Therians, or live-bearing mammals, after divergence from Prototherians "via retrotransposition of a gene on the X chromosome," the authors add.

Finally, published in advance in Nucleic Acids Research this week, researchers in Texas and China say irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture. Using a novel human lung model, the team investigated the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells and found that the kinetic loss of simple double-strand breaks were reduced in organotypic 3D culture compared to kinetics of repair in 2D culture. "Levels of expression of multiple DNA damage repair pathway genes were significantly reduced in the organotypic 3D culture compared with those in 2D culture providing molecular evidence for the defective DNA damage repair in organotypic culture," the authors write. "Further, when differentiated cells with unrepaired DNA lesions re-entered the cell cycle, they manifested a spectrum of gross-chromosomal aberrations in mitosis."

The Scan

Drug Response Variants May Be Distinct in Somatic, Germline Samples

Based on variants from across 21 drug response genes, researchers in The Pharmacogenomics Journal suspect that tumor-only DNA sequences may miss drug response clues found in the germline.

Breast Cancer Risk Gene Candidates Found by Multi-Ancestry Low-Frequency Variant Analysis

Researchers narrowed in on new and known risk gene candidates with variant profiles for almost 83,500 individuals with breast cancer and 59,199 unaffected controls in Genome Medicine.

Health-Related Quality of Life Gets Boost After Microbiome-Based Treatment for Recurrent C. Diff

A secondary analysis of Phase 3 clinical trial data in JAMA Network Open suggests an investigational oral microbiome-based drug may lead to enhanced quality of life measures.

Study Follows Consequences of Early Confirmatory Trials for Accelerated Approval Indications

Time to traditional approval or withdrawal was shorter when confirmatory trials started prior to accelerated approval, though overall regulatory outcomes remained similar, a JAMA study finds.