A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase

A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase
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DOI:
10.1101/gad.1265105
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发表时间:
2005-01-01
影响因子:
10.5
通讯作者:
Gorovsky, MA
Gorovsky, MA
中科院分区:
生物学1区
文献类型:
--
作者:
Mochizuki, K;Gorovsky, MA

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以往的研究表明,四膜虫在接合后期发生的涉及DNA序列消除的基因组重排是由接合早期合成的非基因、异质、双向、微核转录本产生的siRNA样扫描(SCN)RNA表观遗传控制的。在这里,我们证明了Dcl1p是三种四膜虫类酶之一,是将微核转录产物加工成scnRNA所必需的。DCL1也是组蛋白H3在Lys 9甲基化所必需的,在野生型细胞中,这种甲基化专门发生在序列(IESS)被消除时。这些结果表明,Dcl1p将非基因微核转录产物加工成scnRNAs,是消除IES所必需的。这是第一个将非基因微核转录本、scnRNAs和基因组重排联系起来的证据。Dcl1p也是微核染色体有丝分裂和减数分裂正确分离以及减数分裂前期染色体正常配对所必需的,这表明DCL1在调节染色体动力学方面具有多种功能。
Previous studies indicated that genome rearrangement involving DNA sequence elimination that occurs at late stages of conjugation in Tetrahymena is epigenetically controlled by siRNA-like scan (scn) RNAs produced from nongenic, heterogeneous, bidirectional, micronuclear transcripts synthesized at early stages of conjugation. Here, we show that Dcl1p, one of three Tetrahymena Dicer-like enzymes, is required for processing the micronuclear transcripts to scnRNAs. DCL1 is also required for methylation of histone H3 at Lys 9, which, in wild-type cells, specifically occurs on the sequences (IESs) being eliminated. These results argue that Dcl1p processes nongenic micronuclear transcripts to scnRNAs and is required for IES elimination. This is the first evidence linking nongenic micronuclear transcripts, scnRNAs, and genome rearrangement. Dcl1p also is required for proper mitotic and meiotic segregation of micronuclear chromosomes and for normal chromosome alignment in meiotic prophase, suggesting that DCL1 has multiple functions in regulating chromosome dynamics.