Institute of Military Cognition and Brain Sciences, Academy of Military Medicine, Beijing, China.
Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
PLoS Comput Biol. 2021 Apr 16;17(4):e1008918. doi: 10.1371/journal.pcbi.1008918. eCollection 2021 Apr.
Transcript stability is associated with many biological processes, and the factors affecting mRNA stability have been extensively studied. However, little is known about the features related to human long noncoding RNA (lncRNA) stability. By inhibiting transcription and collecting samples in 10 time points, genome-wide RNA-seq studies was performed in human lung adenocarcinoma cells (A549) and RNA half-life datasets were constructed. The following observations were obtained. First, the half-life distributions of both lncRNAs and messanger RNAs (mRNAs) with one exon (lnc-human1 and m-human1) were significantly different from those of both lncRNAs and mRNAs with more than one exon (lnc-human2 and m-human2). Furthermore, some factors such as full-length transcript secondary structures played a contrary role in lnc-human1 and m-human2. Second, through the half-life comparisons of nucleus- and cytoplasm-specific and common lncRNAs and mRNAs, lncRNAs (mRNAs) in the nucleus were found to be less stable than those in the cytoplasm, which was derived from transcripts themselves rather than cellular location. Third, kmers-based protein-RNA or RNA-RNA interactions promoted lncRNA stability from lnc-human1 and decreased mRNA stability from m-human2 with high probability. Finally, through applying deep learning-based regression, a non-linear relationship was found to exist between the half-lives of lncRNAs (mRNAs) and related factors. The present study established lncRNA and mRNA half-life regulation networks in the A549 cell line and shed new light on the degradation behaviors of both lncRNAs and mRNAs.
转录本稳定性与许多生物过程有关，影响 mRNA 稳定性的因素已得到广泛研究。然而，人们对与人类长非编码 RNA（lncRNA）稳定性相关的特征知之甚少。通过抑制转录并在 10 个时间点收集样本，在人类肺腺癌细胞（A549）中进行了全基因组 RNA-seq 研究，并构建了 RNA 半衰期数据集。得出了以下观察结果。首先，具有一个外显子的 lncRNA 和信使 RNA（mRNA）（lnc-human1 和 m-human1）的半衰期分布与具有多个外显子的 lncRNA 和 mRNA（lnc-human2 和 m-human2）的半衰期分布显著不同。此外，一些因素，如全长转录本二级结构，在 lnc-human1 和 m-human2 中发挥了相反的作用。其次，通过核和细胞质特异性和共同的 lncRNA 和 mRNA 的半衰期比较，发现核内的 lncRNA（mRNA）比细胞质内的 lncRNA（mRNA）稳定性差，这是由转录本本身而不是细胞位置决定的。第三，基于 kmers 的蛋白质-RNA 或 RNA-RNA 相互作用极有可能促进 lnc-human1 的 lncRNA 稳定性并降低 m-human2 的 mRNA 稳定性。最后，通过应用基于深度学习的回归，发现 lncRNA（mRNA）的半衰期与相关因素之间存在非线性关系。本研究建立了 A549 细胞系中的 lncRNA 和 mRNA 半衰期调控网络，为 lncRNA 和 mRNA 的降解行为提供了新的见解。
