Department of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), Dolgoprudny, 141701, Russian Federation.
Research Centre for Medical Genetics, Moscow, Russian Federation, 115522.
BMC Genomics. 2019 May 8;20(Suppl 3):298. doi: 10.1186/s12864-019-5538-z.
It was shown that the major part of human genome is transcribed and produces a large number of long noncoding RNAs (lncRNAs). Today there are many evidences that lncRNAs play important role in the regulation of gene expression during different cellular processes. Moreover, lncRNAs are involved in the development of various human diseases. However, the function of the major part of annotated transcripts is currently unknown, whereas different lncRNAs annotations tend to have low overlap. Recent studies revealed that some lncRNAs have small open reading frames (smORFs), that produce the functional microproteins. However, the question whether the function of such genes is determined by microprotein or RNA itself or both remains open. Thus, the study of new lncRNA genes is important to understanding the functional role of such a heterogeneous class of genes.
In the present study, we used reverse transcription PCR and rapid amplification of cDNA ends (RACE) analysis to determine the structure of the LINC01420 transcript. We revealed that LINC01420 has two isoforms that differ in length of the last exon and are localized predominantly in the cytoplasm. We showed that expression of the short isoform is much higher than the long. Besides, MTT and wound-healing assays revealed that LINC01420 inhibited cell migration in human melanoma cell line A375, but does not influence on cell viability.
During our work, D'Lima et al. found smORF in the first exon of the LINC01420 gene. This smORF produces functional microprotein named non-annotated P-body dissociating polypeptide (NoBody). However, our results provide new facts about LINC01420 transcript and its function.
研究表明,人类基因组的大部分都可被转录,并产生大量长非编码 RNA(lncRNA)。目前有大量证据表明,lncRNA 在不同细胞过程中的基因表达调控中发挥着重要作用。此外,lncRNA 还参与了多种人类疾病的发生。然而,目前大部分注释转录本的功能尚不清楚,而不同 lncRNA 的注释往往重叠度较低。最近的研究表明,一些 lncRNA 具有小的开放阅读框(smORF),能够产生功能性的微蛋白。然而,这些基因的功能是由微蛋白还是 RNA 本身或两者共同决定,这个问题仍未解决。因此,研究新的 lncRNA 基因对于理解这类异质性基因的功能作用具有重要意义。
在本研究中,我们使用逆转录 PCR 和快速扩增 cDNA 末端(RACE)分析来确定 LINC01420 转录本的结构。结果显示,LINC01420 有两种不同的亚型,它们在最后一个外显子的长度上存在差异,并且主要定位于细胞质中。我们发现短亚型的表达水平明显高于长亚型。此外,MTT 和划痕愈合实验表明,LINC01420 抑制了人黑色素瘤细胞系 A375 的细胞迁移,但对细胞活力没有影响。
在我们的工作中,D'Lima 等人在 LINC01420 基因的第一个外显子中发现了 smORF。该 smORF 产生了一种功能性的微蛋白,名为非注释 P 体解离多肽(NoBody)。然而,我们的研究结果提供了关于 LINC01420 转录本及其功能的新事实。