Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon.

Transfer RNA halves are found as nicked tRNAs in cells: evidence that nicked tRNAs regulate expression of an RNA repair operon.
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在细胞中发现转移RNA的两半是刻度的TRNA:刻度TRNA调节RNA修复操纵子的表达的证据。

DOI:
10.1261/rna.079575.122
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发表时间:
2023-05
期刊:
RNA
影响因子:
4.5
通讯作者:
Wolin, Sandra L.
Wolin, Sandra L.
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Xinguo;Wolin, Sandra L.

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转移 RNA 片段被认为可以调节真核生物中的许多过程,包括翻译抑制、表观遗传和癌症。在鼠伤寒沙门氏菌中,以 2',3' 环磷酸结尾的 5' tRNA 半部被认为可以结合 RtcR 转录激活因子,从而导致 RNA 修复操纵子的转录。然而,由于 5' 和 3' tRNA 半部在切割后仍可保持碱基配对,因此 5' tRNA 半部可能作为带切口的 tRNA 与 RtcR 结合。在这里,我们报道带切口的 tRNA 是 RtcR 的配体。通过在保留碱基配对的条件下从细菌中分离 RNA,我们发现许多 tRNA 半部都是带切口的 tRNA 的形式。使用模拟切口 tRNA 的循环排列 tRNA,我们发现以 2',3' 环状磷酸结尾的切口 tRNA 是比相应的 5' tRNA 一半更好的 RtcR 配体。在人类细胞中,我们发现一些 tRNA 半部在被反密码子核酸酶切割后仍以带切口的 tRNA 形式保持碱基配对。我们的工作支持 RNA 修复操纵子在修复带切口的 tRNA 中的作用,并对真核生物中 tRNA 片段的功能具有影响。
Transfer RNA fragments are proposed to regulate numerous processes in eukaryotes, including translation inhibition, epigenetic inheritance, and cancer. In the bacterium Salmonella enterica serovar Typhimurium, 5′ tRNA halves ending in 2′,3′ cyclic phosphate are proposed to bind the RtcR transcriptional activator, resulting in transcription of an RNA repair operon. However, since 5′ and 3′ tRNA halves can remain base paired after cleavage, the 5′ tRNA halves could potentially bind RtcR as nicked tRNAs. Here we report that nicked tRNAs are ligands for RtcR. By isolating RNA from bacteria under conditions that preserve base pairing, we show that many tRNA halves are in the form of nicked tRNAs. Using a circularly permuted tRNA that mimics a nicked tRNA, we show that nicked tRNA ending in 2′,3′ cyclic phosphate is a better ligand for RtcR than the corresponding 5′ tRNA half. In human cells, we show that some tRNA halves similarly remain base paired as nicked tRNAs following cleavage by anticodon nucleases. Our work supports a role for the RNA repair operon in repairing nicked tRNAs and has implications for the functions proposed for tRNA fragments in eukaryotes.
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