Tani H, Nakamura Y, Ijiri K, Akimitsu N
Radioisotope Center, The University of Tokyo, Tokyo, Japan.
Drug Discov Ther. 2010 Aug;4(4):235-9.
Recent large-scale transcriptome analyses have revealed a large number of transcripts with low protein-coding potential, known as non-coding RNAs (ncRNAs). Many studies revealed that several long ncRNAs are involved in the regulation of genome organization and gene expression, or in the structural components of functional domains in the nucleus. As regulation of mRNA decay in the cytoplasm is crucial for controlling the abundance of cellular transcripts and the levels of protein expression, so regulation of long non-coding RNA decay in the nucleus is considered to be important for biological function. Although enzymatic pathways involved in cytoplasmic mRNA decay have been studied extensively, far less is known about those in nuclear long ncRNA decay. Here, we have investigated decay of metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), which is a long (~ 8 kb) ncRNA that is misregulated in many human cancers and was shown to be retained specifically in the nucleus in nuclear speckles, as a model of nuclear long ncRNA in mammalian cells. We have found that the half-life of MALAT-1 ranges from ~ 9 h to > 12 h in various cancer cells. Moreover, Xrn2, PM/Scl-75, PARN, and Mtr4, known nuclear RNases or RNA helicases, did not affect MALAT-1 degradation or single knockdown of these components did not change the MALAT-1 decay rate.
近期大规模转录组分析揭示了大量蛋白质编码潜力较低的转录本,即非编码RNA(ncRNA)。许多研究表明,一些长链非编码RNA参与基因组组织和基因表达的调控,或参与细胞核功能域的结构组成。由于细胞质中mRNA降解的调控对于控制细胞转录本丰度和蛋白质表达水平至关重要,因此细胞核中长链非编码RNA降解的调控被认为对生物学功能很重要。尽管细胞质中mRNA降解所涉及的酶促途径已得到广泛研究,但对于细胞核中长链非编码RNA降解的途径却知之甚少。在此,我们以转移相关肺腺癌转录本1(MALAT-1)作为哺乳动物细胞核中长链非编码RNA的模型,对其降解进行了研究。MALAT-1是一种长约8 kb的非编码RNA,在许多人类癌症中表达失调,且特异性地保留在细胞核的核斑中。我们发现,在各种癌细胞中MALAT-1的半衰期约为9小时至超过12小时。此外,已知的细胞核核糖核酸酶或RNA解旋酶Xrn2、PM/Scl-75、PARN和Mtr4均不影响MALAT-1的降解,单独敲低这些成分也不会改变MALAT-1的降解速率。