Basic biology and therapeutic implications of lncRNA.
Basic biology and therapeutic implications of lncRNA.
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DOI：
10.1016/j.addr.2015.05.012
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发表时间：
2015-06-29
影响因子：
16.1
通讯作者：
Wahlestedt C
中科院分区：
文献类型：
--
作者：
Khorkova O;Hsiao J;Wahlestedt C
长链非编码RNA（lncRNA）是最近发现的一类非编码RNA分子，主要是由于FANTOM以及后来的GENCODE和ENCODE财团的努力，在过去十年中一直是研究的热点。深入了解lncRNA生物学的广泛努力已经证明了它们在保护染色体完整性，维持基因组结构，X染色体失活，印记，转录，翻译和表观遗传调控中的多种结构和调节作用。本文就lncRNA生物学领域的最新研究进展作一简要综述，并讨论其在治疗中的意义。A -基因复制和假基因的再利用是lncRNA进化的一条途径。B -移动的遗传元件（MGE）经常引发新转录单位（TU）的形成和进化，其中一些转录单位成为lncRNA。C-lncRNA参与一些基因座转录调控所必需的长距离DNA环. D-lncRNA是维持端粒所必需的. E-lncRNA参与X染色体失活和印迹。F-lncRNA支架和调节核旁斑的形成，因此也控制mRNA的核质转运。G-lncRNA参与染色质间颗粒的形成，使得前mRNA剪接和成熟成为可能。H -表观遗传修饰的精细调节通过表观遗传效应子的拴系和lncRNA形成多梳体来辅助。I -lncRNA的细胞质作用包括mRNA稳定性的正向和负向调节。J-lncRNA参与翻译调控和新生蛋白稳定性的正、负调控. K-lncRNA充当miRNA海绵，阻断miRNA活性。
Long non-coding RNAs (lncRNA), a class of non-coding RNA molecules recently identified largely due to the efforts of FANTOM, and later GENCODE and ENCODE consortia, have been a subject of intense investigation in the past decade. Extensive efforts to get deeper understanding of lncRNA biology have yielded evidence of their diverse structural and regulatory roles in protecting chromosome integrity, maintaining genomic architecture, X chromosome inactivation, imprinting, transcription, translation and epigenetic regulation. Here we wil briefly review the recent studies in the field of lncRNA biology focusing mostly on mammalian species and discuss their therapeutic implications. A - Gene duplication and repurposing of pseudogenes is one of proposed routes of lncRNA evolution. B - Mobile genetic elements (MGE) frequently initate formation and evolution of new transcriptional units (TU) some of which become lncRNA. C – lncRNA participate in long range DNA looping essential for transcription regulation in somce loci. D – lncRNA are essential for telomere maintenance. E – lncRNA participate in X-chromosome inactivation and imprinting. F - lncRNA scaffold and regulate formation of of nuclear paraspeckles, as a result also controlling the nuclear-cytoplasmic transport of mRNA. G – lncRNA are involved in formation of interchromatin granules enabling pre-mRNA splicing and maturation. H - Fine regulation of epigenetic modifications is assisted by tethering of epigenetic effectors and formation of polycomb bodies by lncRNA. I – Cytoplasmic roles of lncRNA include positive and negative regulation of mRNA stability. J – lncRNA are involved in regulation of translation and positive and negative regulation of nascent protein stability. K - lncRNA act as miRNA sponges blocking miRNA activity.