School of Biotechnology and Biomolecular Sciences, UNSW Sydney, 2052, Sydney, Australia.
Epigenetics Chromatin. 2021 Sep 27;14(1):45. doi: 10.1186/s13072-021-00419-2.
It is established that protein-coding exons are preferentially localized in nucleosomes. To examine whether the same is true for non-coding exons, we analysed nucleosome occupancy in and adjacent to internal exons in genes encoding long non-coding RNAs (lncRNAs) in human CD4+ T cells and K562 cells.
We confirmed that internal exons in lncRNAs are preferentially associated with nucleosomes, but also observed an elevated signal from H3K4me3-marked nucleosomes in the sequences upstream of these exons. Examination of 200 genomic lncRNA loci chosen at random across all chromosomes showed that high-density regions of H3K4me3-marked nucleosomes, which we term 'slabs', are associated with genomic regions exhibiting intron retention. These retained introns occur in over 50% of lncRNAs examined and are mostly first introns with an average length of just 354 bp, compared to the average length of all human introns of 6355 and 7987 bp in mRNAs and lncRNAs, respectively. Removal of short introns from the dataset abrogated the high upstream H3K4me3 signal, confirming that the association of slabs and short lncRNA introns with intron retention holds genome-wide. The high upstream H3K4me3 signal is also associated with alternatively spliced exons, known to be prominent in lncRNAs. This phenomenon was not observed with mRNAs.
There is widespread intron retention and clustered H3K4me3-marked nucleosomes in short first introns of human long non-coding RNAs, which raises intriguing questions about the relationship of IR to lncRNA function and chromatin organization.
已有研究证实，蛋白质编码外显子优先定位于核小体中。为了研究非编码外显子是否也存在这种情况，我们分析了人类 CD4+T 细胞和 K562 细胞中长链非编码 RNA（lncRNA）基因内部外显子及其上下游的核小体占有率。
我们证实 lncRNA 内部外显子优先与核小体结合，但也观察到这些外显子上游序列中 H3K4me3 标记核小体的信号升高。对跨越所有染色体随机选择的 200 个基因组 lncRNA 基因座进行检查后发现，高密度 H3K4me3 标记核小体区域，我们称之为“板块”，与表现出内含子保留的基因组区域相关。在检测到的 lncRNA 中，超过 50%的 lncRNA 存在保留内含子，这些保留内含子大多为第一内含子，平均长度仅为 354bp，而 mRNA 和 lncRNA 中所有人类内含子的平均长度分别为 6355bp 和 7987bp。从数据集去除短内含子后，上游 H3K4me3 信号显著降低，证实了板块和短 lncRNA 内含子与内含子保留的关联具有全基因组普遍性。这种高上游 H3K4me3 信号也与已知在 lncRNA 中普遍存在的可变剪接外显子相关。这种现象在 mRNA 中没有观察到。
在人类长链非编码 RNA 的短第一内含子中存在广泛的内含子保留和聚集的 H3K4me3 标记核小体，这提出了关于 IR 与 lncRNA 功能和染色质组织之间关系的有趣问题。
