Mechanisms of Telomerase RNA Processing and Formation of Ribonucleoprotein Particles in Saccharomyces cerevisiae
Final Report Abstract
Recent studies have revealed that splicing can be utilized to regulate gene expression not only positively – as in the conventional scenario – but also negatively. This is the case when inefficient splicing is coupled to degradation of the unspliced RNA or spliced products and was shown to play an important role in down-regulating the levels of functional mRNA; however, the mechanisms involved are not well understood. Thanks to the work carried out while I was supported by the DFG Forschungsstipendium, we now understand how fission yeast combines inefficient splicing of introns with sequence elements contained within the intron that activate nuclear surveillance pathways to regulate the expression of multiple genes. Using CRAC analysis (UV cross-linking and analysis of cDNA) we found the RNA-binding protein Mmi1 to be associated with inefficiently spliced introns. Mmi1 in fission yeast is a well-known developmental regulator that plays an important role in suppressing the meiotic program during mitotic growth. It achieves this by binding to sequence elements in meiotic transcripts, then recruiting the nuclear exosome which rapidly degrades the RNA. In addition, Mmi1 helps to bring the RNA-induced silencing complex to its target genes, resulting in the formation of heterochromatin over the gene locus. Recently, we and others have found that Mmi1 regulates expression of non-meiotic transcripts through its association with non-coding RNAs, e.g. with the prt1 transcript that regulates expression of pho1 acid phosphatase. We have now uncovered an additional role for Mmi1 in regulating the expression of intron-containing mRNAs.
Publications
- (2013) “mRNA quality control goes transcriptional” Biochem Soc Trans. 41(6):1666-72
Kilchert, C., Vasiljeva, L.
- (2013) “Spliceosome-mediated decay (SMD) regulates expression of nonintronic genes in budding yeast” Genes Dev. 27(18):2025-38
Volanakis, A., Passoni, M., Hector R.D., Shah, S., Kilchert, C., Granneman, S., Vasiljeva, L.
- (2014) “lncRNA recruits RNAi and the exosome to dynamically regulate pho1 expression in response to phosphate levels in fission yeast” Genes Dev. 28(3):231-44
Shah, S., Wittmann, S., Kilchert, C., Vasiljeva, L.
(See online at https://doi.org/10.1101/gad.230177.113)
