Translation of upstream open reading frames in a model of neuronal differentiation

Autor: Sang Y. Chun, Peter K. Todd, Caitlin M. Rodriguez, Ryan E. Mills
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0106 biological sciences
Translation
Five prime untranslated region
lcsh:QH426-470
lcsh:Biotechnology
Population
Computational biology
Biology
Ribosome profiling
01 natural sciences
Ribosome
Upstream open reading frame
Models
Biological
03 medical and health sciences
Open Reading Frames
0302 clinical medicine
Ribosomal protein
lcsh:TP248.13-248.65
Cell Line
Tumor
Near-cognate start codon
Genetics
Coding region
Humans
Upstream (networking)
education
Gene
030304 developmental biology
Neurons
education.field_of_study
0303 health sciences
Messenger RNA
Translation (biology)
Cell Differentiation
Open reading frame
lcsh:Genetics
Neuronal differentiation
Gene Expression Regulation
Protein Biosynthesis
5′ untranslated region
Ribosomes
030217 neurology & neurosurgery
Algorithms
010606 plant biology & botany
Biotechnology
Research Article
Zdroj: BMC Genomics
BMC Genomics, Vol 20, Iss 1, Pp 1-18 (2019)
ISSN: 1471-2164
Popis: Background Upstream open reading frames (uORFs) initiate translation within mRNA 5′ leaders, and have the potential to alter main coding sequence (CDS) translation on transcripts in which they reside. Ribosome profiling (RP) studies suggest that translating ribosomes are pervasive within 5′ leaders across model systems. However, the significance of this observation remains unclear. To explore a role for uORF usage in a model of neuronal differentiation, we performed RP on undifferentiated and differentiated human neuroblastoma cells. Results Using a spectral coherence algorithm (SPECtre), we identify 4954 consistently translated uORFs across 31% of all neuroblastoma transcripts. These uORFs predominantly utilize non-AUG initiation codons and exhibit translational efficiencies (TE) comparable to annotated coding regions. On a population basis, the global impact of both AUG and non-AUG initiated uORFs on basal CDS translation were small, even when analysis is limited to conserved and consistently translated uORFs. However, uORFs did alter the translation of a subset of genes, including the Diamond-Blackfan Anemia associated ribosomal gene RPS24. With retinoic acid induced differentiation, we observed an overall positive correlation in translational shifts between uORF/CDS pairs. However, CDSs downstream of uORFs show smaller shifts in TE with differentiation relative to CDSs without a predicted uORF, suggesting that uORF translation buffers cell state dependent fluctuations in CDS translation. Conclusion This work provides insights into the dynamic relationships and potential regulatory functions of uORF/CDS pairs in a model of neuronal differentiation. Electronic supplementary material The online version of this article (10.1186/s12864-019-5775-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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