title: Mechanisms and Developmental Roles of Promoter-proximal Pausing of RNA Polymerase II.
abstract: RNA polymerase II (Pol II) temporarily stops transcription after synthesizing 30-50 bases, and resumes elongation only after stimulations by various signaling molecules and developmental cues. This phenomenon, called promoter-proximal pausing, is observed in 10-50% of the entire genes fromDrosophilaembryos to human cells. Release of paused Pol II is primarily mediated by the activated form of positive transcription elongation factor b (P-TEFb) initially sequestered in the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP) complex. Many proteins and RNAs have been discovered and studied in detail to explain the process of the pausing and release of Pol II in relation to P-TEFb. At the functional level, promoter-proximal pausing regulates genes involved in stimulus-response and development inDrosophila. In mammalian stem cell biology, pausing is important for proliferation and signaling in embryonic stem cells and the formation of induced pluripotent stem cells. Other than this, however, little is known about the biological significance of pausing in mammalian cell differentiation. Further study on pausing mechanisms as well as its functions will contribute to the development of stem cell biology and its clinical applications.
authors.affiliation: Stem Cell Institute, Department of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Stem Cell Institute, Department of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lowe
authors.affiliation: Stem Cell Institute, Department of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Schwartz
authors.affiliation: Stem Cell Institute, Department of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kikyo
keywords: 7SK snRNP; Differentiation; Gene expression; P-TEFb; Promoter; RNA polymerase II; Stem cells