Abstract
Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. However, the mechanism by which they are recognized and targeted to the exosome is not fully understood. Here we report that the MTREC complex, which has recently been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs, is also the major nuclear exosome targeting complex for CUTs and unspliced pre-mRNAs in Schizosaccharomyces pombe. The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of CUTs.
Highlights
Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome
To understand more about the biochemical composition of the MTREC complex, we tagged the genomic copy of Mtl[1] and Red[1] and some of the interacting proteins, including Red[5], Ars[2] and Cbc[1]
Our experiments show that the MTREC complex is recruited to CUTs and meiotic messenger RNAs (mRNAs), and it plays a key role in their degradation by the nuclear exosome
Summary
Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. the mechanism by which they are recognized and targeted to the exosome is not fully understood. The MTREC complex binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. Mtl[1] was recently shown to interact with Red[1], Pab[2], Red[5], Iss[10], Mmi[1] and several additional nuclear proteins[29,30], some of which are related to the subunits of the human CBCN complex This complex, called MTREC (Mtl1–Red[1] core) or NURS (nuclear RNA silencing) complex, is responsible for the degradation of meiotic mRNAs and ncRNAs, and plays a role in the assembly of heterochromatic islands at meiotic genes[29,30,31,32,33]. Our findings establish the MTREC complex as a central component of the eukaryotic RNA surveillance machinery through its role in the recognition and delivery of CUTs and unspliced/mis-spliced pre-mRNAs to the nuclear exosome
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