Nuclear retention element recruits U1 snRNP components to restrain spliced lncRNAs in the nucleus

被引：54
|
作者：
Azam, Sikandar [1 ]
Hou, Shuai [1 ]
Zhu, Baohui [1 ]
Wang, Weijie [1 ]
Hao, Tian [1 ]
Bu, Xiangxue [1 ]
Khan, Misbah [1 ]
Lei, Haixin [1 ]
机构：
[1] Dalian Med Univ, Canc Ctr, Inst Canc Stem Cell, 9 West Sect,Lvshun South Rd, Dalian 116044, Peoples R China
来源：
RNA BIOLOGY | 2019年 / 16卷 / 08期
基金：
中国国家自然科学基金;
关键词：
LncRNA locali?zation; MEG3; nuclear retention element; U1 snRNP components; PRE-MESSENGER-RNAS; NONCODING RNAS; SUBCELLULAR-LOCALIZATION; SEQUENCES; EXPORT;
D O I：
10.1080/15476286.2019.1620061
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In contrast to cytoplasmic localization of spliced mRNAs, many spliced lncRNAs are localized in the nucleus. To investigate the mechanism, we used lncRNA MEG3 as a reporter and mapped a potent nuclear retention element (NRE), deletion of this element led to striking export of MEG3 from the nucleus to the cytoplasm. Insertion of the NRE resulted in nuclear retention of spliced lncRNA as well as spliced mRNA. We further purified RNP assembled on the NRE in vitro and identified the proteins by mass spectrometry. Screen using siRNA revealed depletion of U1 snRNP components SNRPA, SNRNP70 or SNRPD2 caused significant cytoplasmic localization of MEG3 reporter transcripts. Co-knockdown these factors in HFF1 cells resulted in an increased cytoplasmic distribution of endogenous lncRNAs. Together, these data support a model that U1 snRNP components restrain spliced lncRNAs in the nucleus via the interaction with nuclear retention element.
引用
收藏
页码：1001 / 1009
页数：9
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