Landscape of transcription in human cells

Abstract

Summary Eukaryotic cells make many types of primary and processed RNAs that are found either in specific sub-cellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic sub-cellular localizations are also poorly understood. Since RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell’s regulatory capabilities are focused on its synthesis, processing, transport, modifications and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations taken together prompt to a redefinition of the concept of a gene.

The landscape of human mutually exclusive splicing

“…To validate the predicted MXE candidates, we made use of over 15 billion publically available RNA‐Seq reads, selecting 515 samples comprising 31 tissues and organs, 12 cell lines and seven developmental stages (Barbosa‐Morais et al , 2012; Djebali et al , 2012; Tilgner et al , 2012; Xue et al , 2013; Yan et al , 2013; Fagerberg et al , 2014; Dataset EV1). The data were chosen to encompass common and rare potential splice events in a broad range of tissues, cell types and embryonic stages.…”

“…To understand the expression patterns of MXEs, we conducted a differential inclusion analysis using the Human Protein Atlas (Fagerberg et al , 2014), Embryonic Development (Yan et al , 2013) and ENCODE datasets (Djebali et al , 2012). Of the 1,399 MXEs, 608 MXEs (345 unique genes), 573 MXEs (389 unique genes) and 552 MXEs (330 unique genes) are differentially expressed, respectively (adjusted P ‐value < 0.05; Fig 3A, Appendix Figs S23–S26, Dataset EV5 and EV6).…”

Promoter architectures and developmental gene regulation

“…Quantitative nature of CAGE has been used to model expression dynamics and to reconstruct the regulatory networks driving the differentiation [30] and maintaining identity of numerous human and mouse cell and tissue types [27], by identifying key transcription factors binding at promoters. Moreover, CAGE signal has been shown to be enriched at enhancers [35] and has been used to construct an atlas of active enhancers over cells and tissues across the whole human body [36]. Thus, in addition to providing a valuable resource of genome-wide cell type-specific TSSs, which are a more precise alternative to TSS positions available in annotation databases, CAGE is also a powerful approach for studying various aspects of gene regulation.…”

Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage

“…Virtually 60% of the human transcriptome is represented by long RNAs (with length exceeding 200 nucleotides) that lack protein‐coding capacity and are thus referred to as long noncoding RNAs (lncRNAs) 8. LncRNAs play a remarkable role not only in regulating the entire transcriptome by interacting with multiple mRNAs and modulating epigenetic mechanisms but also in posttranslational regulation and direct interference with protein activity 9.…”