Lorenzi Luca E, Bah Amadou, Wischnewski Harry, Shchepachev Vadim, Soneson Charlotte, Santagostino Marco, Azzalin Claus M
Institute of Biochemistry (IBC) Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland.
Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
EMBO J. 2015 Jan 2;34(1):115-29. doi: 10.15252/embj.201489559. Epub 2014 Nov 14.
The telomeric transcriptome comprises multiple long non-coding RNAs generated by transcription of linear chromosome ends. In a screening performed in Schizosaccharomyces pombe, we identified factors modulating the cellular levels of the telomeric transcriptome. Among these factors, Cay1 is the fission yeast member of the conserved family of Cactins, uncharacterized proteins crucial for cell growth and survival. In cay1∆ mutants, the cellular levels of the telomeric factor Rap1 are drastically diminished due to defects in rap1+ pre-mRNA splicing and Rap1 protein stability. cay1∆ cells accumulate histone H3 acetylated at lysine 9 at telomeres, which become transcriptionally desilenced, are over-elongated by telomerase and cause chromosomal aberrations in the cold. Overexpressing Rap1 in cay1+ deleted cells significantly reverts all telomeric defects. Additionally, cay1∆ mutants accumulate unprocessed Tf2 retrotransposon RNA through Rap1-independent mechanisms. Thus, Cay1 plays crucial roles in cells by ultimately harmonizing expression of transcripts originating from seemingly unrelated genomic loci.
端粒转录组包含由线性染色体末端转录产生的多种长链非编码RNA。在对粟酒裂殖酵母进行的一项筛选中，我们鉴定出了调节端粒转录组细胞水平的因子。在这些因子中，Cay1是保守的Cactin家族在裂殖酵母中的成员，该家族是对细胞生长和存活至关重要的未表征蛋白质。在cay1∆突变体中，由于rap1+前体mRNA剪接和Rap1蛋白稳定性存在缺陷，端粒因子Rap1的细胞水平急剧下降。cay1∆细胞在端粒处积累赖氨酸9乙酰化的组蛋白H3，端粒转录沉默被解除，被端粒酶过度延长，并在低温下导致染色体畸变。在缺失cay1+的细胞中过表达Rap1可显著恢复所有端粒缺陷。此外，cay1∆突变体通过不依赖Rap1的机制积累未加工的Tf2逆转座子RNA。因此，Cay1通过最终协调源自看似不相关基因组位点的转录本的表达在细胞中发挥关键作用。
