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Review
. 2008 Mar;14(3):324-30.
doi: 10.1016/j.devcel.2008.02.002.

Intron Delays and Transcriptional Timing During Development

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Free PMC article
Review

Intron Delays and Transcriptional Timing During Development

Ian A Swinburne et al. Dev Cell. .
Free PMC article

Abstract

The time taken to transcribe most metazoan genes is significant because of the substantial length of introns. Developmentally regulated gene networks, where timing and dynamic patterns of expression are critical, may be particularly sensitive to intron delays. We revisit and comment on a perspective last presented by Thummel 16 years ago: transcriptional delays may contribute to timing mechanisms during development. We discuss the presence of intron delays in genetic networks. We consider how delays can impact particular moments during development, which mechanistic attributes of transcription can influence them, how they can be modeled, and how they can be studied using recent technological advances as well as classical genetics.

Figures

Figure 1
Figure 1. Cartoon Depicting Great Length of pre-mRNA in Relation to Processed mRNA
As currently annotated, the average human gene is 95% intronic, and the time it takes to transcribe the considerable length of introns contributes to the time delay during gene expression.
Figure 2
Figure 2. Schematic Depictions of the Behavior Exhibited by Four Genetic Network Motifs Sensitive to Transcriptional Time Delays
(A) In response to a shared transcriptional activator, a longer gene with more intron length will take more time to reach a steady-state expression level than a shorter gene because of the greater time delay during the transcription of its length. (B) In response to a shared transcriptional repressor, the nascent polymerases along a longer gene will take longer to clear, and therefore the duration of expression will be extended. The behavior of this network motif is very dependent on the stabilities of mRNA and proteins. (C) During the cell cycle, RNA polymerase II disengages from chromatin during prophase to late anaphase. Therefore, longer genes will take more time to resume steady-state expression levels during the subsequent cell cycle. (Steady-state expression levels are depicted as being different for visualization purposes). (D) Within an autoinhibitory transcriptional network, the presence of long time periods between transcription initiation and repression by a folded, nuclear repressor destabilizes the system. When the protein and mRNAs are suitably unstable and there exists some cooperativity in how the repressor binds its own promoter, oscillations in expression can occur. The frequency of the oscillations depends on the length of the time delay; therefore, intron length can determine the time interval between expressions.

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