Leonardi Jessica, Box Jessica A, Bunch Jeremy T, Baumann Peter
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA.
Nat Struct Mol Biol. 2008 Jan;15(1):26-33. doi: 10.1038/nsmb1343. Epub 2007 Dec 23.
Telomerase is the ribonucleoprotein complex that adds telomeric repeats to the ends of chromosomes. Its protein subunit TERT is highly conserved among eukaryotes, whereas the RNA subunit varies greatly in size and sequence, hindering the identification of telomerase RNAs in some important model organisms. Here we report the identification and functional characterization of TER1, the telomerase RNA component from fission yeast Schizosaccharomyces pombe. Deletion of ter1+ caused progressive shortening of telomeres and cellular senescence followed by chromosome circularization. Interactions between Est1 and Trt1, the two known protein components of fission yeast telomerase, were dependent on TER1, supporting its role as a scaffold for the assembly of protein subunits. Using a series of template mutations, we show that translocation or dissociation site variability and template-primer slippage account for the sequence heterogeneity of fission yeast telomeres.
端粒酶是一种核糖核蛋白复合体,可将端粒重复序列添加到染色体末端。其蛋白质亚基TERT在真核生物中高度保守,而RNA亚基在大小和序列上差异很大,这阻碍了在一些重要模式生物中鉴定端粒酶RNA。在此,我们报告了来自裂殖酵母粟酒裂殖酵母的端粒酶RNA组分TER1的鉴定及其功能特征。删除ter1+导致端粒逐渐缩短和细胞衰老,随后染色体环化。裂殖酵母端粒酶的两个已知蛋白质组分Est1和Trt1之间的相互作用依赖于TER1,支持了其作为蛋白质亚基组装支架的作用。通过一系列模板突变,我们表明易位或解离位点变异性以及模板-引物滑动导致了裂殖酵母端粒的序列异质性。