Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA.

Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA.
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DOI:
10.1016/j.molcel.2009.06.027
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发表时间:
2009-08-28
期刊:
影响因子:
16
通讯作者:
Carmichael GG
Carmichael GG
中科院分区:
生物学1区
文献类型:
--
作者:
Chen LL;Carmichael GG

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在许多细胞中,在其3′-非翻译区(3′-UTR)中含有反向重复序列(人类中为Alu重复序列)的mRNA不能有效地输出到细胞质中。核保留与腺苷到肌苷编辑相关,并且在含有蛋白质p54 nrb、PSF和PSP 1 α的旁视相关复合物中。我们报告说,人类胚胎干细胞(hESC)中强大的编辑活动不会导致核保留。p54 nrb、PSF和PSP 1 α均在hESCs中表达,但不存在副斑,仅在分化时出现。Paraspeckle的组装和功能取决于一个长的核保留非编码RNA hNEAT 1的表达。这种RNA在hESC中不表达,但在分化时被诱导。在HeLa细胞中hNEAT 1的敲低导致paraspeckles的损失和含有反向Alu重复的mRNA的核质输出增强。两者合计,这些结果分配一个大的非编码核RNA在mRNA输出的调节生物学功能。
In many cells, mRNAs containing inverted repeats (Alu repeats in humans) in their 3′-untranslated regions (3′-UTRs) are inefficiently exported to the cytoplasm. Nuclear retention correlates with adenosine-to-inosine editing and is in paraspeckle-associated complexes containing the proteins p54nrb, PSF and PSP1α. We report that robust editing activity in human embryonic stem cells (hESCs), does not lead to nuclear retention. p54nrb, PSF and PSP1α are all expressed in hESCs, but paraspeckles are absent and only appear upon differentiation. Paraspeckle assembly and function depends on expression of a long nuclear-retained noncoding RNA, hNEAT1. This RNA is not expressed in hESCs, but is induced upon differentiation. Knockdown of hNEAT1 in HeLa cells results both in loss of paraspeckles and enhanced nucleocytoplasmic export of mRNAs containing inverted Alu repeats. Taken together, these results assign a biological function to a large noncoding nuclear RNA in the regulation of mRNA export.
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