Interaction between Ski7p and Upf1p is required for nonsense-mediated 3′-to-5′ mRNA decay in yeast

AUTOR(ES)

Takahashi, Shinya

FONTE

Oxford University Press

RESUMO

Aberrant mRNAs containing premature termination codons (PTC-mRNAs) are degraded by a conserved surveillance system, referred to as the nonsense- mediated decay (NMD) pathway. Although NMD is reported to operate on the decapping and 5′-to-3′ exonucleolytic decay of PTC-mRNAs without affecting deadenylation, a role for an opposite 3′-to-5′ decay pathway remains largely unexplored. In this study, we have characterized the 3′-to-5′ directed mRNA degradation in the yeast NMD pathway. PTC-mRNAs are stabilized in yeast cells lacking the components of 3′-to-5′ mRNA-decay machinery. The 3′-to-5′ directed degradation of PTC-mRNAs proceeds more rapidly than that of the PTC-free transcript, in a manner dependent on the cytoplasmic exosome and Upf proteins. Moreover, Upf1p, but not Upf2p, interacts physically with an N-terminal domain of Ski7p, although the interaction requires Upf2p. The efficiency of 3′-to-5′ directed degradation of PTC-mRNAs is impaired by overexpression of Ski7p N-domain fragments that contain a sequence of the Upf1p-interaction region. These data suggest that the activation of 3′-to-5′ directed NMD is mediated through the interaction between Upf1p and the Ski7p N domain.

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