U7 snRNA 在抑制人细胞中的 HERV1/LTR12s 和 lincRNAs 中的新功能。

Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells.

机构信息

Department of Gene Expression, Laboratory of RNA Processing, Institute of Molecular Biology and Biotechnology, Faculty of Biology and Center for Advanced Technology, Adam Mickiewicz University, Poznan, Poland.

Institute of Human Biology and Evolution, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.

出版信息

Nucleic Acids Res. 2024 Sep 23;52(17):10504-10519. doi: 10.1093/nar/gkae738.

DOI:10.1093/nar/gkae738

PMID:39189459

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11417402/

Abstract

U7 snRNA is part of the U7 snRNP complex, required for the 3' end processing of replication-dependent histone pre-mRNAs in S phase of the cell cycle. Here, we show that U7 snRNA plays another function in inhibiting the expression of a subset of long terminal repeats of human endogenous retroviruses (HERV1/LTR12s) and LTR12-containing long intergenic noncoding RNAs (lincRNAs), both bearing sequence motifs that perfectly match the 5' end of U7 snRNA. We demonstrate that U7 snRNA inhibits LTR12 and lincRNA transcription and propose a mechanism in which U7 snRNA hampers the binding/activity of the NF-Y transcription factor to CCAAT motifs within LTR12 elements. Thereby, U7 snRNA plays a protective role in maintaining the silencing of deleterious genetic elements in selected types of cells.

摘要

U7 snRNA 是 U7 snRNP 复合物的一部分，在细胞周期 S 期，需要其完成复制依赖性组蛋白前体 mRNA 的 3' 端加工。在这里，我们表明 U7 snRNA 在抑制人类内源性逆转录病毒（HERV1/LTR12s）的一部分长末端重复序列和含有 LTR12 的长基因间非编码 RNA（lincRNA）的表达方面发挥了另一项功能，这两者都具有与 U7 snRNA 的 5' 端完全匹配的序列基序。我们证明 U7 snRNA 抑制 LTR12 和 lincRNA 转录，并提出了一种机制，其中 U7 snRNA 阻碍 NF-Y 转录因子与 LTR12 元件内的 CCAAT 基序结合/活性。因此，U7 snRNA 在维持选定类型细胞中有害遗传元件的沉默方面发挥了保护作用。