ACCUMULATION OF MESSENGER-RNA CODING FOR THE CTF13P KINETOCHORE SUBUNIT OF SACCHAROMYCES-CEREVISIAE DEPENDS ON THE SAME FACTORS THAT PROMOTE RAPID DECAY OF NONSENSE MESSENGER-RNAS

The CTF13 gene codes for a subunit of the kinetochore in Saccharomyces cerevisiae. The temperature-sensitive mutation ctf13-30, which confer s reduced fidelity of chromosome transmission, is a G --> A transition causing an amino acid substitution of Lys for Glu(146). Strains carry ing one chromosomal copy of ctf13-30 fail to grow at the restrictive t emperature, whereas a haploid strain carrying two copies of ctf13- 30 can grow. Four genes, UPF1, UPF2, UPF3 and ICK1, were represented amon g extragenic suppressors of ctf13-30. The UPF genes encode proteins th at promote rapid decay of pre-mRNAs and mRNAs containing a premature s top codon. Suppressor mutations in these genes restore kinetochore fun ction by causing increased accumulation of ctf13-30 mRNA. They also ca use increased accumulation of CYH2 pre-mRNA, which is a natural target of UPF-mediated decay. Mutations in ICK1 restore kinetochore function but have no effect on ctf13-30 mRNA or CYH2 pre-mRNA accumulation. Mo st importantly, loss of UPF1 function causes increased accumulation of wild-type CTF13 mRNA but has no effect on the mRNA half-life. We prop ose that UPF-mediated decay modulates the mRNA level of one or more fa ctors involved in CTF13 mRNA expression.