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Yeast Sm-like proteins function in mRNA decapping and decay

Abstract

One of the main mechanisms of messenger RNA degradation in eukaryotes occurs by deadenylation-dependent decapping which leads to 5′-to-3′ decay1,2. A family of Sm-like (Lsm) proteins has been identified, members of which contain the ‘Sm’ sequence motif, form a complex with U6 small nuclear RNA and are required for pre-mRNA splicing3,4,5,6,7,8,9. Here we show that mutations in seven yeast Lsm proteins (Lsm1–Lsm7) also lead to inhibition of mRNA decapping. In addition, the Lsm1–Lsm7 proteins co-immunoprecipitate with the mRNA decapping enzyme (Dcp1), a decapping activator (Pat1/Mrt1) and with mRNA. This indicates that the Lsm proteins may promote decapping by interactions with the mRNA and the decapping machinery. In addition, the Lsm complex that functions in mRNA decay appears to be distinct from the U6-associated Lsm complex, indicating that Lsm proteins form specific complexes that affect different aspects of mRNA metabolism.

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Figure 1: MFA2pG mRNA is stabilized in most lsm mutant strains.
Figure 2: Lsm mutants accumulate oligoadenylated, full-length capped mRNAs.
Figure 3: Lsm proteins co-immunoprecipitate with proteins involved in mRNA decay.
Figure 4: Lsm proteins and Dcp1 co-immunoprecipitate mRNA.
Figure 5: Cellular localization of Dcp1, Pat1/Mrt1, Lsm7 and Lsm1 by immunofluorescence analysis.

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Acknowledgements

We thank members of R.P.'s laboratory for useful discussions and comments on the manuscript. This study was supported by funds from the Howard Hughes Medical Institute, the NIH, a Wellcome Trust Prize Studentship to A.E.M. and a Royal Society Cephalosporin Fund Senior Research Fellowship to J.D.B. We also thank N. Rodriquez-Cousino for the antisera to Pat1, C. Russell for providing the HA–lsy1 strain and A. Sachs for the anti-Lsm1 antibodies.

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Correspondence to Roy Parker.

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Tharun, S., He, W., Mayes, A. et al. Yeast Sm-like proteins function in mRNA decapping and decay. Nature 404, 515–518 (2000). https://doi.org/10.1038/35006676

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