lncRNA BC200 被加工成稳定的 Alu 单体。

IF 4.2 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RNA Pub Date : 2024-10-16 DOI:10.1261/rna.080152.124
Evan P Booy, Daniel Gussakovsky, Mira Brown, Rowan Shwaluk, Mark W Nachtigal, Sean A McKenna
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引用次数: 0

摘要

非编码 RNA BC200 在人类癌症中含量升高,与翻译调控以及细胞存活和增殖有关。在 BC200 过表达时,我们观察到第二种更小的 RNA 的相关表达。这种 RNA 是内源表达的,与 BC200 相比具有细胞类型依赖性变异。色聚体标记表达构建物证实该 RNA 是 BC200 的截短形式,测序显示其模态长度为 120 nt,因此我们将该 RNA 片段称为 BC120。我们介绍了准确特异检测 BC120 的方法,并确定 BC120 在多种正常人体组织中表达,在卵巢癌中也会升高。与 BC200 相比,BC120 表现出显著的稳定性,并能抵抗针对 BC200 3' 独特序列的基因敲除策略。与单独敲除BC200相比,联合敲除BC200和BC120会产生更大的表型影响,而且过表达BC120会对GFP报告物的翻译产生负面影响。BC200存在一种新的、截短的和稳定的形式,这增加了研究这种非编码RNA的复杂性,在未来对BC200和其他相关Alu RNA的研究中必须考虑到这一点。
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lncRNA BC200 is processed into a stable Alu monomer.

The noncoding RNA BC200 is elevated in human cancers and is implicated in translation regulation as well as cell survival and proliferation. Upon BC200 overexpression, we observed correlated expression of a second, smaller RNA species. This RNA is expressed endogenously and exhibits cell-type-dependent variability relative to BC200. Aptamer-tagged expression constructs confirmed that the RNA is a truncated form of BC200, and sequencing revealed a modal length of 120 nt; thus, we refer to the RNA fragment as BC120. We present a methodology for accurate and specific detection of BC120 and establish that BC120 is expressed in several normal human tissues and is also elevated in ovarian cancer. BC120 exhibits remarkable stability relative to BC200 and is resistant to knockdown strategies that target the 3' unique sequence of BC200. Combined knockdown of BC200 and BC120 exhibits greater phenotypic impacts than knockdown of BC200 alone, and overexpression of BC120 negatively impacts translation of a GFP reporter, providing insight into a potential translational regulatory role for this RNA. The presence of a novel, truncated, and stable form of BC200 adds complexity to the investigation of this noncoding RNA that must be considered in future studies of BC200 and other related Alu RNAs.

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来源期刊
RNA
RNA 生物-生化与分子生物学
CiteScore
8.30
自引率
2.20%
发文量
101
审稿时长
2.6 months
期刊介绍: RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
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