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真核细胞中带有 snoRNA(slb-snoRNA)的稳定套索:向导 RNA 的调控水平。

Stable lariats bearing a snoRNA (slb-snoRNA) in eukaryotic cells: A level of regulation for guide RNAs.

机构信息

Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.

Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218

出版信息

Proc Natl Acad Sci U S A. 2021 Nov 9;118(45). doi: 10.1073/pnas.2114156118.

Abstract

Small nucleolar (sno)RNAs guide posttranscriptional modifications essential for the biogenesis and function of their target. The majority of snoRNAs in higher eukaryotes are encoded within introns. They are first released from nascent transcripts in the form of a lariat and rapidly targeted by the debranching enzyme and nuclear exonucleases for linearization and further trimming. In this study, we report that some snoRNAs are encoded within unusually stable intronic RNAs. These intronic sequences can escape the debranching enzyme and accumulate as lariats. Stable lariats bearing a snoRNA, or slb-snoRNA, are associated with snoRNA binding proteins but do not guide posttranscriptional modification. While most slb-snoRNAs accumulate in the nucleus, some can be exported to the cytoplasm. We find that this export competes with snoRNA maturation. Slb-snoRNAs provide a previously unknown layer of regulation to snoRNA and snoRNA binding proteins.

摘要

小核仁 RNA(snoRNA)指导对其靶标生物发生和功能至关重要的转录后修饰。高等真核生物中的大多数 snoRNA 都编码在内含子中。它们最初以套索的形式从新生转录本中释放出来,并迅速被解分支酶和核外切核酸酶靶向,以进行线性化和进一步修剪。在这项研究中,我们报告说,一些 snoRNA 编码在异常稳定的内含子 RNA 中。这些内含子序列可以逃避解分支酶的作用,并积累为套索。带有 snoRNA 的稳定套索,或 slb-snoRNA,与 snoRNA 结合蛋白相关联,但不指导转录后修饰。虽然大多数 slb-snoRNA 在核内积累,但有些可以输出到细胞质中。我们发现这种输出与 snoRNA 成熟竞争。Slb-snoRNA 为 snoRNA 和 snoRNA 结合蛋白提供了一个以前未知的调控层。

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