دورية أكاديمية

Cytoplasmic long noncoding RNAs are differentially regulated and translated during human neuronal differentiation.

التفاصيل البيبلوغرافية
العنوان: Cytoplasmic long noncoding RNAs are differentially regulated and translated during human neuronal differentiation.
المؤلفون: Douka K; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom., Birds I; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom., Wang D; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom., Kosteletos A; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom., Clayton S; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom., Byford A; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom., Vasconcelos EJR; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom., O'Connell MJ; School of Life Sciences, Faculty of Medicine and Health Sciences, The University of Nottingham, Nottingham NG7 2UH, United Kingdom., Deuchars J; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom.; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom., Whitehouse A; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom.; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom., Aspden JL; School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.; LeedsOmics, University of Leeds, Leeds LS2 9JT, United Kingdom.
المصدر: RNA (New York, N.Y.) [RNA] 2021 Sep; Vol. 27 (9), pp. 1082-1101. Date of Electronic Publication: 2021 Jun 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9509184 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-9001 (Electronic) Linking ISSN: 13558382 NLM ISO Abbreviation: RNA Subsets: MEDLINE
أسماء مطبوعة: Publication: <2003->: Cold Spring Harbor, NY : Cold Spring Harbor Laboratory Press
Original Publication: New York, NY : Cambridge University Press, c1995-
مواضيع طبية MeSH: Protein Biosynthesis*, Cell Differentiation/*genetics , Neurons/*metabolism , Polyribosomes/*genetics , RNA, Long Noncoding/*genetics, Base Sequence ; Brain/growth & development ; Brain/metabolism ; Brain/pathology ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cytoplasm/genetics ; Cytoplasm/metabolism ; Humans ; Neurons/cytology ; Open Reading Frames ; Polyribosomes/metabolism ; RNA, Long Noncoding/classification ; RNA, Long Noncoding/metabolism ; Sequence Analysis, RNA ; Tretinoin/pharmacology
مستخلص: 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.
(© 2021 Douka et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)
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معلومات مُعتمدة: MR/N000471/1 United Kingdom MRC_ Medical Research Council; BB/M011151/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; MR/N013840/1 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: lncRNA; neuronal differentiation; polysome; ribosome profiling; translation
المشرفين على المادة: 0 (RNA, Long Noncoding)
5688UTC01R (Tretinoin)
تواريخ الأحداث: Date Created: 20210701 Date Completed: 20210930 Latest Revision: 20210930
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8370745
DOI: 10.1261/rna.078782.121
PMID: 34193551
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-9001
DOI:10.1261/rna.078782.121