Abstract
Introns impact several vital aspects of eukaryotic organisms like proteomic plasticity, genomic stability, stress response and gene expression. A role for introns in the regulation of gene expression at the level of transcription has been known for more than thirty years. The molecular basis underlying the phenomenon, however, is still not entirely clear. An important clue came from studies performed in budding yeast that indicate that the presence of an intron within a gene results in formation of a multi-looped gene architecture. When looping is defective, these interactions are abolished, and there is no enhancement of transcription despite normal splicing. In this review, we highlight several potential mechanisms through which looping interactions may enhance transcription. The promoter-5′ splice site interaction can facilitate initiation of transcription, the terminator-3′ splice site interaction can enable efficient termination of transcription, while the promoter-terminator interaction can enhance promoter directionality and expedite reinitiation of transcription. Like yeast, mammalian genes also exhibit an intragenic interaction of the promoter with the gene body, especially exons. Such promoter-exon interactions may be responsible for splicing-dependent transcriptional regulation. Thus, the splicing-facilitated changes in gene architecture may play a critical role in regulation of transcription in yeast as well as in higher eukaryotes.
Highlights
Introns are intervening non-coding sequences in eukaryotic genes that are removed from the primary transcripts by the process of splicing (Figure 1)
Splicing factors do not contact DNA directly, but proximity of splice sites on RNA with the corresponding DNA region during cotranscriptional splicing results in splicing factors getting crosslinked to the splice sites on DNA as well (Kotovic et al, 2003; Lin et al, 2008; Oesterreich et al, 2016; Minocha et al, 2018; Nojima et al, 2018). This evidence suggests that the intron-mediated gene loop formation is due to an interaction of the initiation and termination factors occupying distal ends of a gene with splicing factors bound to the intronic regions
Clear from the studies described above that intron-dependent looped gene architecture likely plays a crucial role in enhancement of transcription in budding yeast
Summary
Introns are intervening non-coding sequences in eukaryotic genes that are removed from the primary transcripts by the process of splicing (Figure 1). The physical interaction of the promoter and terminator regions of a gene during transcription results in the formation of a looped gene architecture (Ansari and Hampsey, 2005). Activator-dependent gene looping has been shown to enhance transcription by facilitating direct transfer of polymerase from the terminator to the promoter for reinitiation, and by enhancing promoter directionality (Tan-Wong et al, 2012; Al Husini et al, 2013).
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