Small RNA-mediated regulation of DNA dosage in the ciliate Oxytricha.

Small RNA-mediated regulation of DNA dosage in the ciliate Oxytricha.
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DOI:
10.1261/rna.061333.117
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发表时间:
2018-01
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Landweber LF
Landweber LF
中科院分区:
其他
文献类型:
--
作者:
Khurana JS;Clay DM;Moreira S;Wang X;Landweber LF

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Dicer依赖性小非编码RNA在多种生物的基因调控中发挥重要作用。内源性小干扰RNA(siRNA)是植物和动物中古老的转座子控制途径的一部分。纤毛虫,Oxytricha trifallax,在其体细胞核中有大约16,000个基因大小的染色体。长的非编码RNA在性发育开始时建立高倍性水平,但在细胞分裂和生长期间调节染色体拷贝数的因素一直是个谜。我们报道了一类Dicer(Dcl-1)和RNA依赖性RNA聚合酶(RdRP)依赖的内源性小RNA在O.三叶草无性生长的种群表达丰富的一类21-nt的sRNA,映射到大多数染色体的编码和非编码区。这些sRNA与染色质结合,并且它们的水平令人惊讶地与mRNA水平不相关。相反,这些小RNA的水平与基因组DNA拷贝数相关。dcl-1或rdrp突变体中sRNA水平的降低导致染色体拷贝数的伴随减少。此外,这些细胞没有显示转座子激活的迹象,而是显示不规则的核结构和复制应激的迹象。总之,来自体细胞核的Oxytricha Dcl-1和RdRP依赖性小RNA有助于维持基因剂量,可能通过DNA复制中的作用,为这些小RNA在真核生物中提供了新的作用。
Dicer-dependent small noncoding RNAs play important roles in gene regulation in a wide variety of organisms. Endogenous small interfering RNAs (siRNAs) are part of an ancient pathway of transposon control in plants and animals. The ciliate, Oxytricha trifallax, has approximately 16,000 gene-sized chromosomes in its somatic nucleus. Long noncoding RNAs establish high ploidy levels at the onset of sexual development, but the factors that regulate chromosome copy numbers during cell division and growth have been a mystery. We report a novel function of a class of Dicer (Dcl-1)- and RNA-dependent RNA polymerase (RdRP)-dependent endogenous small RNAs in regulating chromosome copy number and gene dosage in O. trifallax. Asexually growing populations express an abundant class of 21-nt sRNAs that map to both coding and noncoding regions of most chromosomes. These sRNAs are bound to chromatin and their levels surprisingly do not correlate with mRNA levels. Instead, the levels of these small RNAs correlate with genomic DNA copy number. Reduced sRNA levels in dcl-1 or rdrp mutants lead to concomitant reduction in chromosome copy number. Furthermore, these cells show no signs of transposon activation, but instead display irregular nuclear architecture and signs of replication stress. In conclusion, Oxytricha Dcl-1 and RdRP-dependent small RNAs that derive from the somatic nucleus contribute to the maintenance of gene dosage, possibly via a role in DNA replication, offering a novel role for these small RNAs in eukaryotes.
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