MEN ε/β nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles
MEN ε/β nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles
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DOI：
10.1101/gr.087775.108
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发表时间：
2009-03-01
期刊：
影响因子：
7
通讯作者：
Spector, David L.
中科院分区：
文献类型：
--
作者：
Sunwoo, Hongjae;Dinger, Marcel E.;Spector, David L.
对人类和小鼠基因组转录产物的研究表明，产生的转录物比预测的蛋白质编码基因所能解释的要多得多。使用自定义的微阵列，我们已经确定了184个非编码RNA，表现出超过两倍的上调或下调分化成肌管的C2 C12成肌细胞。在这里，我们专注于Men β/β基因座，其在分化期间上调3.3倍。两种非编码RNA同种型由单个RNA聚合酶II启动子产生，其3'末端的位置不同。Men β是一种3.2-kb的多聚腺苷酸化RNA，而Men β是一种类似于20-kb的转录物，在其3 '端含有基因组编码的富含poly（A）的片段。Men β的3 '-末端由RNase P切割产生。Men β/β转录本定位于核旁斑，并直接与NONO相互作用。MEN β/β表达的敲低导致核旁斑的破坏。此外，在通过DRB处理从转录抑制释放后，旁斑的形成在MEN β/β耗尽的细胞中被抑制。我们的研究结果表明，MEN β/β非编码RNA是paraspeckles的重要结构/组织成分。
Studies of the transcriptional output of the human and mouse genomes have revealed that there are many more transcripts produced than can be accounted for by predicted protein-coding genes. Using a custom microarray, we have identified 184 non-coding RNAs that exhibit more than twofold up- or down-regulation upon differentiation of C2C12 myoblasts into myotubes. Here, we focus on the Men epsilon/beta locus, which is up- regulated 3.3-fold during differentiation. Two non-coding RNA isoforms are produced from a single RNA polymerase II promoter, differing in the location of their 3' ends. Men epsilon is a 3.2-kb polyadenylated RNA, whereas Men beta is an similar to 20-kb transcript containing a genomically encoded poly(A)-rich tract at its 3'-end. The 3'-end of Men beta is generated by RNase P cleavage. The Men epsilon/beta transcripts are localized to nuclear paraspeckles and directly interact with NONO. Knockdown of MEN epsilon/beta expression results in the disruption of nuclear paraspeckles. Furthermore, the formation of paraspeckles, after release from transcriptional inhibition by DRB treatment, was suppressed in MEN epsilon/beta-depleted cells. Our findings indicate that the MEN epsilon/beta non-coding RNAs are essential structural/organizational components of paraspeckles.