Overproduction of non-translatable mRNA silences. The transcription of Ty1 retrotransposons in S. cerevisiae via functional inactivation of the nuclear cap-binding complex and subsequent hyperstimulation of the TORC1 pathway.

Co-suppression is high gene copy number-triggered homology-dependent gene silencing, and co-suppression may have evolved in eukaryotes to counter invasive molecular parasites, such as viruses and transposons. We previously reported 'Ty1 transcriptional co-suppression'-high Ty1 copy number-triggered transient transcriptional silencing of Ty1 retrotransposons in S. cerevisiae. We report here that this phenomenon is unlikely to be homology-dependent, despite the copy number dependence. The Ty1 mRNA is an extremely poor template for translation, and overproduction of non-translatable mRNA without Ty1 homology is sufficient to initiate the transient Ty1 transcriptional silencing. We present genetic evidence that overproduction of non-translatable mRNA may functionally inactivate the nuclear cap-binding complex (CBC), and inactivation of CBC may then hyperstimulate the TORC1 pathway to mediate Ty1 transcriptional silencing. Our results point to a potent regulatory function of non-translatable mRNA in vivo (via CBC and TORC1) to potentially modulate a variety of intracellular activities, such as Ty1 transcription. Although overproduction of non-translatable mRNA causes transient Ty1 transcriptional silencing, it does not play a detectable role in controlling Ty1 retrotransposition.