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lncRNA BC200 被加工成稳定的 Alu 单体。

lncRNA BC200 is processed into a stable Alu monomer.

机构信息

Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2.

Department of Biochemistry and Medical Genetics, Gynecology and Reproductive Sciences, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0J9.

出版信息

RNA. 2024 Oct 16;30(11):1477-1494. doi: 10.1261/rna.080152.124.

Abstract

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.

摘要

非编码 RNA BC200 在人类癌症中升高,并与翻译调节以及细胞存活和增殖有关。在 BC200 过表达时,我们观察到第二种较小的 RNA 物种的相关表达。这种 RNA 是内源性表达的,与 BC200 相比具有细胞类型依赖性的可变性。适配体标记的表达构建体证实该 RNA 是 BC200 的截断形式,测序显示其模式长度为 120 个核苷酸;因此,我们将该 RNA 片段称为 BC120。我们提出了一种用于准确和特异性检测 BC120 的方法,并确定 BC120 在几种正常人类组织中表达,并且在卵巢癌中也升高。BC120 相对于 BC200 表现出显著的稳定性,并且对针对 BC200 的 3'独特序列的敲低策略具有抗性。BC200 和 BC120 的联合敲低比单独敲低 BC200 表现出更大的表型影响,并且 BC120 的过表达对 GFP 报告基因的翻译产生负面影响,为该 RNA 的潜在翻译调节作用提供了见解。新型、截断和稳定的 BC200 形式的存在增加了对该非编码 RNA 的研究的复杂性,在未来对 BC200 和其他相关 Alu RNA 的研究中必须考虑到这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c67/11482611/08af39fdab36/1477f01.jpg

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