RNA 3' end Processing by the Nuclear Exosome Controls NAB2 mRNA Levels.
Kelly Roth, Maria Wolff, Marie Rossi, Scott Butler
Microbiology and Immunology, University of Rochester, 601 Elmwood Ave., Rochester, NY, 14642, USA
The RNA processing exosome is a complex of riboexonucleases required for 3' end formation of some non-coding RNAs and for the degradation of mRNAs in eukaryotes. The nuclear form of the exosome functions in a mRNA surveillance pathway that retains and degrades improperly processed precursor mRNAs within the nucleus. We report here that the nuclear exosome controls the level of NAB2 mRNA, encoding a nuclear poly(A)+ RNA binding protein. Cis-and trans-acting mutations that inhibit degradation by the nuclear exosome subunit Rrp6p result in elevated levels of NAB2 mRNA. Regulation occurs posttranscriptionally and requires a sequence of 26 consecutive adenosines (A26) in the NAB2 3' UTR, which represses NAB2 3' end formation and sensitizes the transcript to degradation by the Rrp6p. Analysis of NAB2 transcripts in exosome mutants suggests that 3' end formation occurs by core exosome trimming of a 3' extended transcript to the A26 sequence, followed by either polyadenylation or degradation by Rrp6p. Nab2p may accelerate the degradation of its own transcript since we find that high copy expression of Nab2p lowers the level of a chimeric NAB2 reporter in an A26-dependent manner. These findings show that; (i) the nuclear exosome controls the concentration of NAB2 mRNA, (ii) its 3' end formation may occur by competition between exosome degradation and polyadenylation and (iii) Nab2p may autoregulate its own expression by accelerating the degradation of NAB2 mRNA.
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