RRM
2010 Rustbelt RNA Meeting
RRM
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Poster abstracts
Abstract:
Gene expression is regulated at many different levels, including post-transcriptionally. One such regulatory mechanism involves nonsense-mediated decay (NMD), a cellular quality control pathway that selectively degrades mRNAs with premature termination codons (PTCs). NMD targets two populations of transcripts: 1) abnormal mRNAs that arise due to mutations or processing errors; and 2) physiological targets—those mRNAs that are targeted in wild type cells as part of normal regulation of gene expression (Neu-Yilik and Kulozik, 2008). One such target is Aly-3, a nuclear export factor found in the nematode C. elegans. Primarily nuclear, Aly-3 binds to RNA transcripts and transports them from the nucleus to the cytoplasm. Using microarrays, RT-PCR, and qRT-PCR, we showed aly-3 to be alternatively spliced. Our results demonstrate the presence of an alternative splice form of aly-3 in worms that could not perform NMD. This isoform is absent in wild-type animals, suggesting that NMD participates in the regulation of the pool of aly-3 transcripts. There are a number of testable models that explain the functional utility of this kind of NMD-dependent splicing. For example, Aly-3 may control its own levels through a homeostatic feedback loop in which the Aly-3 protein drives spicing in an unproductive direction. Such a loop plays a role in the expression of ribosomal protein L12 and the splicing factor SC35, natural targets of mRNA surveillance in C. elegans (Mitrovich and Anderson, 2000; Sureau et al., 2001). Regulatory patterns such as these are consistent with current models that propose widespread coupling of NMD and alternative splicing (Lareau et al., 2007). Alternatively, there may be certain cellular or environmental conditions that lead to NMD-dependent splicing of aly-3 (and others). Predictions made by these different models are currently being tested.
References:
Lareau LF, Brooks AN, Soergel DA, Meng Q, and Brenner SE. The coupling of alternative splicing and nonsense-mediated mRNA decay. Adv Exp Med Biol. 2007; 623:190-211.
Mitrovich QM and Anderson P. Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. Genes Dev. 2000; 14(17):2173-84.
Neu-Yilik G and Kulozik AE. NMD: multitasking between mRNA surveillance and modulation of gene expression. Adv Genet. 2008; 62:185-243.
Sureau A, Gattoni R, Dooghe Y, Stévenin J, Soret J. SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs. EMBO J. 2001; 20(7):1785-96.
Keywords: NMD, alternative splicing, C elegans
