Translational control of intron splicing in eukaryotes

Abstract

Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.

Novel Types of Ca2+ Release Channels Participate in the Secretory Cycle of Paramecium Cells

“…40. Cells were counted daily, and division rates were determined by calculating the number of cell fissions per day.…”

The Y Chromosome Modulates Splicing and Sex-Biased Intron Retention Rates in Drosophila

“…IR is the dominant AS type in Drosophila (GRAVELEY et al 2011) and affects about half of all introns in mammals (WONG et al 2013;BRAUNSCHWEIG et al 2014;EDWARDS et al 2016;PIMENTEL et al 2016). The "anomalous" mRNA generated by the retention of an intron may contain a premature termination codon (PTC) (JAILLON et al 2008), which can sometimes result in the degradation of the mRNA by the nonsense-mediated mRNA decay (NMD) pathway. Because of this, mRNAs generated through IR events could be viewed as failures of the splicing process and void of biological function (JAILLON et al 2008;ROY AND IRIMIA 2008).…”

Quantitative RNA-seq meta analysis of alternative exon usage in C. elegans

“…In eukaryotes, the accumulation of aberrantly spliced messengers that could encode potentially deleterious truncated proteins is prevented by Nonsense Mediated Decay (NMD) (Jaillon et al, 2008, Farlow et al, 2010. Species devoid of NMD tend to almost entirely lack introns (Lynch, 2006) indicating that an error proof splicing system has not arisen through natural evolution (or is yet to be discovered).…”