Genome-wide analysis of lncRNA stability in human

Abstract

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.

Comprehensive analysis of lncRNA-mRNAs co-expression network identifies potential lncRNA biomarkers in cutaneous squamous cell carcinoma

“…LncRNA is a class of nucleotides that transcription length are more than 200 nt and which have little or no protein-coding capability [ 5 , 31 , 32 ]. These molecules play crucial roles in several aspects of biological functions as chromatin remodeling, gene transcription level regulation and protein modification during the occurrence and development of many diseases [ 33 , 34 ]. An increasing number of studies described that dysregulated lncRNA expression is associated with various cancers and may contribute to tumorigenesis, metastasis and prognosis of many tumors [ 35 ].…”

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

“…However, lncRNA NEAT1 is destabilized by AUF1 [ 19 ] and PABPN1 [ 20 ] but stabilized by SPSF1 [ 21 ] through different mechanisms. Interestingly, one recent genome-wide analysis of lncRNA half-lives in humans revealed that RBP-lncRNA interactions mainly enhance the stability of lncRNA with only one exon [ 22 ]. Additionally, N6-methyladenosine (m6A) writers and erasers, as well as readers, are all RBPs that modulate m6A modification and function of lncRNAs [ 23 ], primarily by affecting their stability and changing their expression levels [ 24 , 25 , 26 ].…”

mRNA Vaccines: Why Is the Biology of Retroposition Ignored?

“…An additional property that influences the likelihood of vaccine mRNA genome integration is the stability of vaccine mRNA molecules. The turnover of endogenous mRNA molecules in eukaryotic cells shows great variability, with an estimated average half-life of around 7 h [138]. The precise measurements of the vaccine mRNA half-life in cells are not publicly available [1,2], but it is clear that the sequence and codon optimization of vaccine mRNAs increases their functional half-life with an aim to improve their translation efficiency [6,10,27,56,138,139].…”

“…The turnover of endogenous mRNA molecules in eukaryotic cells shows great variability, with an estimated average half-life of around 7 h [138]. The precise measurements of the vaccine mRNA half-life in cells are not publicly available [1,2], but it is clear that the sequence and codon optimization of vaccine mRNAs increases their functional half-life with an aim to improve their translation efficiency [6,10,27,56,138,139]. Undoubtedly, this prolonged functional half-life increases the chances that vaccine mRNAs encounter L1 machinery and eventually retropose into the genome (Table 1).…”