In Nature this week, a duo from Pennsylvania State University presents new data describing the genomic organization of human transcript initiation complexes. Noting that only a small part of the human genome is coding despite pervasive transcription, the researchers asked whether non-coding transcription arises at promoters, and investigated the interaction of the initiation factors TATA box binding protein, transcription factor IIB, and RNA polymerase II. Among the findings was the identification of about 160,000 transcription initiation complexes across the human K562 genome, and more in other cancer genomes. They note that only about 5 percent of those associated with mRNA genes with the rest associating with non-polyadenylated non-coding transcription.
Meanwhile, in Nature Biotechnology, a multi-institute group of European investigators discuss the results of an initiative to understand the sources of technical and inter-laboratory variation in RNA sequencing. Through the GEUVADIS, or Genetic European Variation in Disease, consortium, the scientists sequenced mRNAs and small RNAs of lymphoblastoid cell lines of 465 individuals in seven sequencing centers, with a large number of replicates. They found the variation between labs to be smaller than the "already limited biological variation," and determined that lab effects "mainly seen in differences in insert size and GC content and could be adequately corrected for." Meanwhile, miRNA content differed widely between samples owing to competitive sequencing of rRNA fragments, but did not affect the relative quantification of mIRNAs. The scientists also provided a set of quality measures and guidelines for assessing technical biases in RNA-seq data.
In a related Nature article, the GEUVADIS consortium reports that the mRNA-seq and microRNA-seq results from those 465 lymphoblastoid cell lines indicate that there is widespread variation affecting the regulation of most human genes. In addition, the consortium reports that it was able to characterize causal regulatory variation and trace it to cellular mechanisms. That ability, the researchers added, will help future predictions of the implications of variants unearthed through personal genome sequencing.
GenomeWeb Daily News has more on the GEUVADIS papers here.