Cytoplasmic Degradation of Splice-Defective Pre-mRNAs and Intermediates

Abstract

Specific systems of nuclear RNA degradation appear to target and degrade aberrant pre-mRNA molecules. In this work we report on a Dbr1p-dependent RNA decay pathway that limits the accumulation of splice-defective lariat intermediates stalled at the second step of splicing. In this pathway, splice-defective lariat intermediates are debranched by Dbr1p and subsequently degraded 5′ to 3′ primarily by the cytoplasmic exonuclease, Xrn1p. When debranching is blocked, these splicing intermediates can be degraded in a 3′ to 5′ direction in a manner dependent on Ski2p, a cofactor for the cytoplasmic exosome. In that Xrn1p and Ski2p are cytoplasmic and Dbr1p localizes to both the nucleus and the cytoplasm, these data suggest that this decay pathway occurs within the cytoplasm. Furthermore, the finding that lariat intermediates accumulate in the dbr1Δ strain suggests that this pathway also functions as an inherent quality control mechanism for the process of pre-mRNA splicing.