Academic journal article Genetics

Introns Regulate RNA and Protein Abundance in Yeast

Academic journal article Genetics

Introns Regulate RNA and Protein Abundance in Yeast

Article excerpt

ABSTRACT

The purpose of introns in the architecturally simple genome of Saccharomyces cerevisiae is not well understood. To assay the functional relevance of introns, a series of computational analyses and several detailed deletion studies were completed on the intronic genes of S. cerevisiae. Mining existing data from genomewide studies on yeast revealed that intron-containing genes produce more RNA and more protein and are more likely to be haplo-insufficient than nonintronic genes. These observations for all intronic genes held true for distinct subsets of genes including ribosomal, nonribosomal, duplicated, and nonduplicated. Corroborating the result of computational analyses, deletion of introns from three essential genes decreased cellular RNA levels and caused measurable growth defects. These data provide evidence that introns improve transcriptional and translational yield and are required for competitive growth of yeast.

THE genes of complex organisms depend on introns to provide regulatory sequences that allow for accurate pre-mRNA processing and alternative splicing. In multicellular organisms most genes contain at least one intron, usually more. In humans, for instance, 94% of the genes are interrupted by, on average, seven introns (LANDER et al. 2001; VENTER et al. 2001). Although splicing is closely coupled to several other processes during gene expression, it is still widely thought that the primary fitness benefits that introns confer to a species are through improved evolution via exon shuf- fling and increased proteome complexity by alternative splicing. On the basis of our observations we propose that introns confer an additional advantage: they improve the transcriptional and translational output of the genes they populate.

The spliceosome, which removes introns from the coding mRNA, is a large cellular complex containing hundreds of proteins and at least five small nuclear RNAs. It is closely coupled to, and in some cases directly interacts with, the proteins responsible for transcription, capping, polyadenylation, RNA export, and nonsensemediated decay (MANIATIS and REED 2002). Given the extensive coupling of splicing with mRNA metabolism, it is not surprising that removing the introns from genes in higher eukaryotes (where intron-containing genes predominate) disrupts mRNA synthesis and often lowers cytoplasmic mRNA levels. The question arises: Are the introns directly responsible for increasing gene expression or does their removal act indirectly, by simply derailing the mRNA synthesis assembly line? Some examples in metazoans support a direct role in expression: introns containing transcriptional enhancers have been identified (SLECKMAN et al. 1996) and one group showed that removing introns from a gene disrupts nucleosome binding (LIU et al. 1995). There is, however, no consensus that introns serve to increase gene expression. To investigate the role that introns may play in cellular fitness we studied their genetic contribution to the fitness of Saccharomyces cerevisiae.

In contrast to multicellular organisms, only 5% of S. cerevisiae genes are interrupted by introns (most by a single intron) and all are constitutively removed during gene expression (AST 2004; BALAKRISHNAN et al. 2005). Evolutionarily, hemiascomycetous yeast have experienced a massive reduction in introns (as well as numerous genes involved in splicing) as compared to Schizosaccharomyces pombe and other ancient ascomycetes (ARAVIND et al. 2000; BON et al. 2003). It could be interpreted that the introns in S. cerevisiae are nucleic acid relics that have yet to be removed by evolution (FINK 1987). This view is mitigated by the observations that the majority (71%) of S. cerevisiae ribosomal genes contain introns and these intron-containing ribosomal genes produce ~24% of cellular RNA (ARES et al. 1999). Thus, arguments have been made that introns may somehow be integral to ribosome biogenesis in yeast (BON et al. …

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