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Analysis of eukaryotic lincRNA sequences reveals signatures of repressed translation in species under strong selection
bioRxiv - Genomics Pub Date : 2021-07-20 , DOI: 10.1101/737890
Anneke Brümmer , Rene Dreos , Ana Claudia Marques , Sven Bergmann

Long intergenic non-coding RNAs (lincRNAs) represent a large fraction of transcribed loci in eukaryotic genomes. Although classified as non-coding, most lincRNAs contain open reading frames (ORFs), and it remains unclear why cytoplasmic lincRNAs are not or very inefficiently translated. Here, we analysed signatures of repressed translation in lincRNA sequences from six eukaryotes. In species under stronger selection, i.e. fission yeast and worm, we detected significantly shorter ORFs than in intronic and non-transcribed control regions, a suboptimal sequence context around start codons for translation initiation, and trinucleotides ('codons') corresponding to less abundant tRNAs than codons in control regions, potentially impeding translation elongation. We verified that varying tRNA expression levels affect ribosome-binding to lincRNAs by analyzing data from five human cell lines. Notably, for three cell lines, codons in abundant cytoplasmic lincRNAs corresponded to lower expressed tRNAs than control codons, substantiating cell type-specific repression of lincRNA translation in human. Finally, comparing non-coding with peptide-encoding ORFs suggested that codon usage at the start of ORFs to be of particular relevance for ribosome-binding. The identified sequence signatures may assist distinguishing peptide- from real non-coding lincRNAs in a cell.

中文翻译:

真核 lincRNA 序列分析揭示了强选择下物种中抑制翻译的特征

长基因间非编码 RNA (lincRNA) 代表了真核基因组中大部分转录基因座。尽管被归类为非编码,但大多数 lincRNA 都包含开放阅读框 (ORF),目前尚不清楚为什么细胞质 lincRNA 没有翻译或翻译效率很低。在这里,我们分析了来自六个真核生物的 lincRNA 序列中抑制翻译的特征。在更强选择下的物种中,即裂殖酵母和蠕虫,我们检测到明显短于内含子和非转录控制区域的 ORF,翻译起始起始密码子周围的次优序列上下文,以及对应于较少丰度 tRNA 的三核苷酸(“密码子”)比控制区域中的密码子,可能会阻碍翻译延伸。我们通过分析来自五种人类细胞系的数据证实了不同的 tRNA 表达水平会影响核糖体与 lincRNA 的结合。值得注意的是,对于三种细胞系,丰富的细胞质 lincRNA 中的密码子对应于比对照密码子表达更低的 tRNA,证实了人类 lincRNA 翻译的细胞类型特异性抑制。最后,将非编码与编码肽的 ORF 进行比较表明,ORF 开始时的密码子使用与核糖体结合特别相关。鉴定的序列特征可能有助于区分细胞中的肽和真正的非编码 lincRNA。最后,将非编码与编码肽的 ORF 进行比较表明,ORF 开始时的密码子使用与核糖体结合特别相关。鉴定的序列特征可能有助于区分细胞中的肽和真正的非编码 lincRNA。最后,将非编码与编码肽的 ORF 进行比较表明,ORF 开始时的密码子使用与核糖体结合特别相关。鉴定的序列特征可能有助于区分细胞中的肽和真正的非编码 lincRNA。
更新日期:2021-07-20
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