Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.
Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.
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DOI：
10.1016/j.molcel.2021.07.004
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发表时间：
2021-09-02
期刊：
影响因子：
16
通讯作者：
Lawrence JB
中科院分区：
文献类型：
--
作者：
Creamer KM;Kolpa HJ;Lawrence JB
核染色体转录的RNA远多于编码蛋白质所需的RNA。在这里，我们调查是否非编码RNA广泛有助于细胞学规模的染色体领土架构。我们开发了一种程序，从细胞核中耗尽可溶性蛋白质，染色质和大多数核RNA，但不使XIST（一种已知的结构RNA）从不溶性染色体“支架”上离域。RNA-seq分析显示，核支架中的大多数RNA是重复丰富的，非编码的，并且主要来源于新生转录物的内含子。不溶性的富含重复序列的（C 0 T-1）RNA与已知的支架蛋白（包括支架附着因子A（SAF-A））共分布，并且这些组分的分布与正常和实验操作的细胞核中的染色质致密化负相关。我们进一步表明，RNA是必需的SAF-A与染色质相互作用，并为丰富的结构嵌入的“支架附着区”普遍存在于常染色质。总的来说，结果表明，长的新生成绩单有助于动态的结构作用，促进活跃的染色体领土的开放架构。Creamer等人报道，长新生转录物中的非编码、富含重复序列在间期染色体结构中起动态结构作用。结合核分级分离，RNA测序和分子细胞学，结果表明不溶性核RNA平台的非染色质支架，是不可或缺的开放架构的活性染色体领土。
Nuclear chromosomes transcribe far more RNA than required to encode protein. Here we investigate whether non-coding RNA broadly contributes to cytological-scale chromosome territory architecture. We develop a procedure that depletes soluble proteins, chromatin and most nuclear RNA from the nucleus, but does not delocalize XIST, a known architectural RNA, from an insoluble chromosome “scaffold.” RNA-seq analysis reveals most RNA in the nuclear scaffold is repeat-rich, non-coding, and predominantly derived from introns of nascent transcripts. Insoluble, repeat-rich (C0T-1) RNA co-distributes with known scaffold proteins including scaffold attachment factor A (SAF-A) and distribution of these components inversely correlates with chromatin compaction in normal and experimentally manipulated nuclei. We further show that RNA is required for SAF-A to interact with chromatin and for enrichment of structurally embedded “scaffold-attachment regions” prevalent in euchromatin. Collectively, results indicate that long nascent transcripts contribute a dynamic structural role which promotes the open architecture of active chromosome territories. Creamer et al. report that non-coding, repeat-rich sequences in long nascent transcripts play a dynamic structural role in interphase chromosome architecture. Combining nuclear fractionation, RNA-sequencing and molecular cytology, results indicate insoluble nuclear RNAs platform a non-chromatin scaffold that is integral to open architecture of active chromosome territories.
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