Accumulation of mRNA Coding for the Ctf13p Kinetochore Subunit of Saccharomyces cerevisiae Depends on the Same Factors That Promote Rapid Decay of Nonsense mRNAs

[摘要] The CTF13 gene codes for a subunit of the kinetochore in Saccharomyces cerevisiae. The temperature-sensitive mutation ctf13-30 , which confers reduced fidelity of chromosome transmission, is a G → A transition causing an amino acid substitution of Lys for Glu146. Strains carrying one chromosomal copy of ctf13-30 fail to grow at the restrictive temperature, whereas a haploid strain carrying two copies of ctf13-30 can grow. Four genes, UPF1, UPF2, UPF3 , and ICK1 , were represented among extragenic suppressors of ctf13-30. The UPF genes encode proteins that promote rapid decay of pre-mRNAs and mRNAs containing a premature stop codon. Suppressor mutations in these genes restore kinetochore function by causing increased accumulation of ctf13-30 mRNA. They also cause 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. Most importantly, loss of UPF1 function causes increased accumulation of wild-type CTF13 mRNA but has no effect on the mRNA half-life. We propose that UPF -mediated decay modulates the mRNA level of one or more factors involved in CTF13 mRNA expression.

[学科分类] 医学（综合）