title: Regulation of alternative splicing at the single-cell level.
abstract: Alternative splicing is a key cellular mechanism for generating distinct isoforms, whose relative abundances regulate critical cellular processes. It is therefore essential that inclusion levels of alternative exons be tightly regulated. However, how the precision of inclusion levels among individual cells is governed is poorly understood. Using single-cell gene expression, we show that the precision of inclusion levels of alternative exons is determined by the degree of evolutionary conservation at their flanking intronic regions. Moreover, the inclusion levels of alternative exons, as well as the expression levels of the transcripts harboring them, also contribute to this precision. We further show that alternative exons whose inclusion levels are considerably changed during stem cell differentiation are also subject to this regulation. Our results imply that alternative splicing is coordinately regulated to achieve accuracy in relative isoform abundances and that such accuracy may be important in determining cell fate.
authors.affiliation: The Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Faigenbloom
authors.affiliation: The Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nimrod D
authors.initials: ND
authors.lastname: Rubinstein
authors.affiliation: The Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kloog
authors.affiliation: The Department of Molecular Biology and Ecology of Plants, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Mayrose
authors.affiliation: The Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel talp@tau.ac.il reuvens@post.tau.ac.il.
authors.forename: Tal
authors.initials: T
authors.lastname: Pupko
authors.affiliation: The Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel talp@tau.ac.il reuvens@post.tau.ac.il.
authors.forename: Reuven
authors.initials: R
authors.lastname: Stein
mesh_terms: D017398:Alternative Splicing; D002454:Cell Differentiation; D019143:Evolution, Molecular; D005091:Exons; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015894:Genome, Human; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000378:metabolism*; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000166:cytology
chemical_list: D012333:RNA, Messenger
keywords: alternative splicing; evolutionary conservation; inclusion level; single cell; splicing regulation