Natural antisense RNA promotes 3' end processing and maturation of MALAT1 lncRNA.
Natural antisense RNA promotes 3' end processing and maturation of MALAT1 lncRNA.
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DOI：
10.1093/nar/gkw047
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发表时间：
2016-04-07
影响因子：
14.9
通讯作者：
Prasanth KV
中科院分区：
文献类型：
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作者：
Zong X;Nakagawa S;Freier SM;Fei J;Ha T;Prasanth SG;Prasanth KV
RNase P介导的核酸内切酶切割在MALAT 1的3′端加工和细胞积累中起着至关重要的作用，MALAT 1是一种促进恶性肿瘤的核保留长非编码RNA。这种裂解事件的调节在很大程度上是不确定的。在这里，我们描述了MALAT 1基因座上广泛表达的天然反义转录物，命名为TALAM 1，它通过促进MALAT 1 RNA的3′端切割和成熟来正向调节MALAT 1水平。TALAM 1 RNA优先定位于转录位点，并且也与MALAT 1 RNA相互作用。TALAM 1的缺失导致3′端切割反应的缺陷，并损害MALAT 1的细胞积累。相反，TALAM 1的过表达促进了反式切割反应。有趣的是，TALAM 1也受到MALAT 1在转录和RNA稳定性水平上的正调控。总之，我们的数据证明了一种新的前馈正调控环，该环的建立是为了维持MALAT 1的高细胞水平，并且还揭示了细胞lncRNA的正义-反义介导的调控机制的存在，这些lncRNA显示RNase P介导的3′端加工。
The RNase P-mediated endonucleolytic cleavage plays a crucial role in the 3′ end processing and cellular accumulation of MALAT1, a nuclear-retained long noncoding RNA that promotes malignancy. The regulation of this cleavage event is largely undetermined. Here we characterize a broadly expressed natural antisense transcript at the MALAT1 locus, designated as TALAM1, that positively regulates MALAT1 levels by promoting the 3′ end cleavage and maturation of MALAT1 RNA. TALAM1 RNA preferentially localizes at the site of transcription, and also interacts with MALAT1 RNA. Depletion of TALAM1 leads to defects in the 3′ end cleavage reaction and compromises cellular accumulation of MALAT1. Conversely, overexpression of TALAM1 facilitates the cleavage reaction in trans. Interestingly, TALAM1 is also positively regulated by MALAT1 at the level of both transcription and RNA stability. Together, our data demonstrate a novel feed-forward positive regulatory loop that is established to maintain the high cellular levels of MALAT1, and also unravel the existence of sense-antisense mediated regulatory mechanism for cellular lncRNAs that display RNase P-mediated 3′ end processing.