Perfect timing: splicing and transcription rates in living cells. (21st November 2016)

• Record Type: Journal Article
• Authors: Alpert, Tara; Herzel, Lydia; Neugebauer, Karla M.
• Is Part Of: Wiley interdisciplinary reviews. Volume 8:Number 2(2017:Mar./Apr.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-11-21
• Subjects: RNA -- Periodicals; 572.8805
• DOI: 10.1002/wrna.1401
• Languages: English
• ISSNs: 1757-7004

Abstract

Abstract : An important step toward understanding gene regulation is the elucidation of the time necessary for the completion of individual steps. Measurement of reaction rates can reveal potential nodes for regulation. For example, measurements of in vivo transcription elongation rates reveal regulation by DNA sequence, gene architecture, and chromatin. Pre‐mRNA splicing is regulated by transcription elongation rates and vice versa, yet the rates of RNA processing reactions remain largely elusive. Since the 1980s, numerous model systems and approaches have been used to determine the precise timing of splicing in vivo . Because splicing can be co‐transcriptional, the position of Pol II when splicing is detected has been used as a proxy for time by some investigators. In addition to these 'distance‐based' measurements, 'time‐based' measurements have been possible through live cell imaging, metabolic labeling of RNA, and gene induction. Yet splicing rates can be convolved by the time it takes for transcription, spliceosome assembly and spliceosome disassembly. The variety of assays and systems used has, perhaps not surprisingly, led to reports of widely differing splicing rates in vivo . Recently, single molecule RNA‐seq has indicated that splicing occurs more quickly than previously deduced. Here we comprehensively review these findings and discuss evidence that splicing and transcription rates are closely coordinated, facilitating the efficiency of gene expression. On the other hand, introduction of splicing delays through as yet unknown mechanisms provide opportunity for regulation. More work is needed to understand how cells optimize the rates of gene expression for a range of biological conditions. WIREs RNA 2017, 8:e1401. doi: 10.1002/wrna.1401 This article is categorized under: RNA-Based Catalysis > RNA Catalysis in Splicing and Translation RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Processing > Splicing Mechanisms Abstract : Schematic showing the progress of RNA polymerase II (Pol II) along the length of gene containing an intron (blue, top panel). The nascent RNA undergoes co‐transcriptional, capping splicing and polyadenylation cleavage. The association of spliceosomal components with the ends of the intron is represented by the presence of the red balls, and the exon‐exon junction is marked by a line. This review revisits a multitude of methods that measure in vivo splicing rates with respect to kilobasepair distance (ruler) from the 3' splice site (SS) or in units of time (clock, lower panel).