RIP-PEN-seq identifies a class of kink-turn RNAs as splicing regulators
RIP-PEN-seq identifies a class of kink-turn RNAs as splicing regulators
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DOI：
10.1038/s41587-023-01749-0
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发表时间：
2023-04-10
影响因子：
46.9
通讯作者：
Yang，Jianhua
中科院分区：
文献类型：
--
作者：
Li，Bin;Liu，Shurong;Yang，Jianhua
扭结转角（K 转角）是一种三维 RNA 结构，存在于所有三个主要系统发育域中。在这项研究中，我们开发了 RIP-PEN-seq 方法来鉴定 K 转角结合蛋白 15.5K 结合的 RNA 全长序列，并在人类和小鼠体内发现了一类先前未表征的具有反向 K 转角基序 (bktRNA) 的 RNA。所有 bktRNA 在其固定末端位置共享两个共有序列基序，并具有复杂的折叠特性、表达和进化模式。我们发现高度保守的 bktRNA1 引导甲基转移酶 fibrillarin 对人类 U12 小核 RNA 进行 RNA 甲基化。 bktRNA1 的缺失会损害 ZCRB1 向小剪接体的募集，从而导致 U12 型内含子的整体剪接失调。大多数 bktRNA 通过与 15.5K 蛋白相互作用来调节局部内含子的剪接。总而言之，我们的研究结果描述了一类小 RNA 的特征，并揭示了基因表达调控的另一层，涉及 bktRNA、RNA 剪接和 RNA 甲基化之间的串扰。
A kink-turn (K-turn) is a three-dimensional RNA structure that exists in all three primary phylogenetic domains. In this study, we developed the RIP-PEN-seq method to identify the full-length sequences of RNAs bound by the K-turn binding protein 15.5K and discovered a previously uncharacterized class of RNAs with backward K-turn motifs (bktRNAs) in humans and mice. All bktRNAs share two consensus sequence motifs at their fixed terminal position and have complex folding properties, expression and evolution patterns. We found that a highly conserved bktRNA1 guides the methyltransferase fibrillarin to install RNA methylation of U12 small nuclear RNA in humans. Depletion of bktRNA1 causes global splicing dysregulation of U12-type introns by impairing the recruitment of ZCRB1 to the minor spliceosome. Most bktRNAs regulate the splicing of local introns by interacting with the 15.5K protein. Taken together, our findings characterize a class of small RNAs and uncover another layer of gene expression regulation that involves crosstalk among bktRNAs, RNA splicing and RNA methylation.