title: Splicing in the human brain.
abstract: It has become increasingly clear over the past decade that RNA has important functions in human cells beyond its role as an intermediate translator of DNA to protein. It is now known that RNA plays highly specific roles in pathways involved in regulatory, structural, and catalytic functions. The complexity of RNA production and regulation has become evident with the advent of high-throughput methods to study the transcriptome. Deep sequencing has revealed an enormous diversity of RNA types and transcript isoforms in human cells. The transcriptome of the human brain is particularly interesting as it contains more expressed genes than other tissues and also displays an extreme diversity of transcript isoforms, indicating that highly complex regulatory pathways are present in the brain. Several of these regulatory proteins are now identified, including RNA-binding proteins that are neuron specific. RNA-binding proteins also play important roles in regulating the splicing process and the temporal and spatial isoform production. While significant progress has been made in understanding the human transcriptome, many questions still remain regarding the basic mechanisms of splicing and subcellular localization of RNA. A long-standing question is to what extent the splicing of pre-mRNA is cotranscriptional and posttranscriptional, respectively. Recent data, including studies of the human brain, indicate that splicing is primarily cotranscriptional in human cells. This chapter describes the current understanding of splicing and splicing regulation in the human brain and discusses the recent global sequence-based analyses of transcription and splicing.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Ammar
authors.initials: A
authors.lastname: Zaghlool
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Ameur
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cavelier
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: lars.feuk@igp.uu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
mesh_terms: D001483:Base Sequence / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D012326:RNA Splicing / Q000502:physiology*; D059467:Transcriptome / Q000502:physiology*
keywords: Alternative splicing; Brain transcriptome; Cotranscriptional splicing; RNA sequencing