title: Widespread Inducible Transcription Downstream of Human Genes.
abstract: Pervasive transcription of the human genome generates RNAs whose mode of formation and functions are largely uncharacterized. Here, we combine RNA-seq with detailed mechanistic studies to describe a transcript type derived from protein-coding genes. The resulting RNAs, which we call DoGs for downstream of gene containing transcripts, possess long non-coding regions (often >45 kb) and remain chromatin bound. DoGs are inducible by osmotic stress through an IP3 receptor signaling-dependent pathway, indicating active regulation. DoG levels are increased by decreased termination of the upstream transcript, a previously undescribed mechanism for rapid transcript induction. Relative depletion of polyA signals in DoG regions correlates with increased levels of DoGs after osmotic stress. We detect DoG transcription in several human cell lines and provide evidence for thousands of DoGs genome wide.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Vilborg
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Passarelli
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Therese A
authors.initials: TA
authors.lastname: Yario
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Kazimierz T
authors.initials: KT
authors.lastname: Tycowski
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015894:Genome, Human; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D009997:Osmotic Pressure; D011061:Poly A / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D053496:Inositol 1,4,5-Trisphosphate Receptors; D062085:RNA, Long Noncoding; D011061:Poly A; D012313:RNA; D011189:Potassium Chloride