title: Dynamic microRNA gene transcription and processing during T cell development.
abstract: By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although various cloning studies have shown that many miRNAs are expressed during T cell development, and in a dynamic manner, it was unclear how comprehensive these earlier analyses were. We therefore decided to profile miRNA expression by next generation sequencing. Furthermore, we profiled miRNA expression starting from the hematopoietic stem cell. This analysis revealed that miRNA expression during T cell development is extremely dynamic, with 645 miRNAs sequenced, and the expression of some varying by as much as 3 orders of magnitude. Furthermore, changes in precursor processing led to altered mature miRNA sequences. We also analyzed the structures of the primary miRNA transcripts expressed in T cells and found that many were extremely long. The longest was pri-mir-29b-1/29a at ∼168 kb. All the long pri-miRNAs also displayed extensive splicing. Our findings indicate that miRNA expression during T cell development is both a highly dynamic and a highly regulated process.
authors.affiliation: Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Francis F
authors.initials: FF
authors.lastname: Kirigin
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lindstedt
authors.forename: Maclean
authors.initials: M
authors.lastname: Sellars
authors.forename: Maria
authors.initials: M
authors.lastname: Ciofani
authors.forename: Siao Li
authors.initials: SL
authors.lastname: Low
authors.forename: Lachlan
authors.initials: L
authors.lastname: Jones
authors.forename: Fiona
authors.initials: F
authors.lastname: Bell
authors.forename: Florencia
authors.initials: F
authors.lastname: Pauli
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
authors.forename: Mark M W
authors.initials: MM
authors.lastname: Chong
mesh_terms: D000818:Animals; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D015723:Gene Library; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000235:genetics / Q000502:physiology; D017423:Sequence Analysis, RNA; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors; C509781:Dicer1 protein, mouse; C513400:Drosha protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases