Cytoplasmic long non-coding RNAs are differentially regulated and translated during human neuronal differentiation
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ABSTRACT:
PROVIDER: PRJNA699598 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14760769.fastq.gz | Fastqsanger.gz | |||
| SRR14760770.fastq.gz | Fastqsanger.gz | |||
| SRR14760771.fastq.gz | Fastqsanger.gz | |||
| SRR14760772.fastq.gz | Fastqsanger.gz | |||
| SRR14760773.fastq.gz | Fastqsanger.gz |
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Project description:The expression of long non-coding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SH5Y cells. We discovered 237 cytoplasmic lncRNAs upregulated during early neuronal differentiation, 58-70% of which are associated with polysome translation complexes. Amongst these polysome associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. 15/45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea suggesting they are under strong selective constraint in this clade. Profiling of publicly available datasets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localises to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a non-canonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.
2021-07-16 | GSE166214 | GEO
Project description:The expression of long noncoding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SY5Y cells. We discovered 237 cytoplasmic lncRNAs up-regulated during early neuronal differentiation, 58%-70% of which are associated with polysome translation complexes. Among these polysome-associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. Fifteen of 45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea, suggesting they are under strong selective constraint in this clade. The profiling of publicly available data sets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development, and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localizes to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells, indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a noncanonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.
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Project description:Long non-coding RNAs (lncRNAs) transcribed in mammals and eukaryotes were thought to have no protein coding capability. However, recent studies have suggested that plenty of lncRNAs are mis-annotated and virtually contain coding sequences which are translated into functional peptides by ribosomal machinery, and these functional peptides are called micropeptides or small peptides. Here we review the rapidly advancing field of micropeptides translated from putative lncRNAs, describe the strategies for their identification, and elucidate their critical roles in many fundamental biological processes. We also discuss the prospects of research in micropeptides and the potential applications of micropeptides.
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Project description:Despite being predicted to lack coding potential, cytoplasmic long non-coding (lnc)RNAs can associate with ribosomes. However, the landscape and biological relevance of lncRNAs translation remains poorly studied. In yeast, cytoplasmic Xrn1-sensitive lncRNAs (XUTs) are targeted by the Nonsense-Mediated mRNA Decay (NMD), suggesting a translation-dependent degradation process. Here, we report that XUTs are pervasively translated, which impacts their decay. We show that XUTs globally accumulate upon translation elongation inhibition, but not when initial ribosome loading is impaired. Ribo-Seq confirmed ribosomes binding to XUTs and identified ribosome-associated 5’-proximal small ORFs. Mechanistically, the NMD-sensitivity of XUTs mainly depends on the 3’-untranslated region length. Finally, we show that the peptide resulting from the translation of an NMD-sensitive XUT reporter exists in NMD-competent cells. Our work highlights the role of translation in the post-transcriptional metabolism of XUTs. We propose that XUT-derived peptides could be exposed to the natural selection, while NMD restricts XUTs levels.
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