A Nuclear Surveillance Pathway for mRNAs with Defective Polyadenylation

Abstract

The pap1-5 mutation in poly(A) polymerase causes rapid depletion of mRNAs at restrictive temperatures. Residual mRNAs are polyadenylated, indicating that Pap1-5p retains at least partial activity. In pap1-5 strains lacking Rrp6p, a nucleus-specific component of the exosome complex of 3′-5′ exonucleases, accumulation of poly(A)⁺ mRNA was largely restored and growth was improved. The catalytically inactive mutant Rrp6-1p did not increase growth of the pap1-5 strain and conferred much less mRNA stabilization than rrp6Δ. This may indicate that the major function of Rrp6p is in RNA surveillance. Inactivation of core exosome components, Rrp41p and Mtr3p, or the nuclear RNA helicase Mtr4p gave different phenotypes, with accumulation of deadenylated and 3′-truncated mRNAs. We speculate that slowed mRNA polyadenylation in the pap1-5 strain is detected by a surveillance activity of Rrp6p, triggering rapid deadenylation and exosome-mediated degradation. In wild-type strains, assembly of the cleavage and polyadenylation complex might be suboptimal at cryptic polyadenylation sites, causing slowed polyadenylation.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/.

ACKNOWLEDGMENTS

We thank P. J. Preker, T. Wiederkehr, and W. Keller for generously providing the pap1-2 and pap1-5 strains and communicating unpublished results; J. S. Butler for kindly providing the rrp6-1 strain; and the laboratory of A. Jacquier, in which some of the experiments were carried out.

C.T. was the recipient of a fellowship from FEBS. This work was supported by the Wellcome Trust and EU grant QLG2-CT-2001-01554.