Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation
Summary: Translation initiation is often attributed as the rate-determining step of eukaryotic protein synthesis and key to gene expression control. Despite this centrality, the series of steps involved in this process is poorly understood. Here, we capture the transcriptome-wide occupancy of riboso...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-04-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720304344 |
| _version_ | 1818492920086396928 |
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| author | Adam Giess Yamila N. Torres Cleuren Håkon Tjeldnes Maximilian Krause Teshome Tilahun Bizuayehu Senna Hiensch Aniekan Okon Carston R. Wagner Eivind Valen |
| author_facet | Adam Giess Yamila N. Torres Cleuren Håkon Tjeldnes Maximilian Krause Teshome Tilahun Bizuayehu Senna Hiensch Aniekan Okon Carston R. Wagner Eivind Valen |
| author_sort | Adam Giess |
| collection | DOAJ |
| description | Summary: Translation initiation is often attributed as the rate-determining step of eukaryotic protein synthesis and key to gene expression control. Despite this centrality, the series of steps involved in this process is poorly understood. Here, we capture the transcriptome-wide occupancy of ribosomes across all stages of translation initiation, enabling us to characterize the transcriptome-wide dynamics of ribosome recruitment to mRNAs, scanning across 5′ UTRs and stop codon recognition, in a higher eukaryote. We provide mechanistic evidence for ribosomes attaching to the mRNA by threading the mRNA through the small subunit. Moreover, we identify features that regulate the recruitment and processivity of scanning ribosomes and redefine optimal initiation contexts. Our approach enables deconvoluting translation initiation into separate stages and identifying regulators at each step. : Giess et al. introduce RCP-seq, a method to study small ribosomal subunit (SSU) dynamics in zebrafish. It reveals threading as the main mode of recruitment to the mRNA and quantifies the impact of sequence features that affect SSU processivity. By contrasting scanning to translating ribosomes, the study calculates initiation rates and redefines the optimal translation initiation context for zebrafish. Keywords: translation, RNA, ribosome profiling, next-generation sequencing, small ribosomal subunit (SSU), scanning processivity, initiation, ribosome recruitment, uORF, Kozak sequence |
| first_indexed | 2024-12-10T17:48:35Z |
| format | Article |
| id | doaj.art-92fbded58f204b49b134c2f10cedc223 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T17:48:35Z |
| publishDate | 2020-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-92fbded58f204b49b134c2f10cedc2232022-12-22T01:39:08ZengElsevierCell Reports2211-12472020-04-01313Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation InitiationAdam Giess0Yamila N. Torres Cleuren1Håkon Tjeldnes2Maximilian Krause3Teshome Tilahun Bizuayehu4Senna Hiensch5Aniekan Okon6Carston R. Wagner7Eivind Valen8Computational Biology Unit, Department of Informatics, University of Bergen, Bergen 5020, NorwayComputational Biology Unit, Department of Informatics, University of Bergen, Bergen 5020, Norway; Corresponding authorComputational Biology Unit, Department of Informatics, University of Bergen, Bergen 5020, NorwayComputational Biology Unit, Department of Informatics, University of Bergen, Bergen 5020, Norway; Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen 5008, NorwayComputational Biology Unit, Department of Informatics, University of Bergen, Bergen 5020, NorwaySars International Centre for Marine Molecular Biology, University of Bergen, Bergen 5008, NorwayDepartment Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USADepartment Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USAComputational Biology Unit, Department of Informatics, University of Bergen, Bergen 5020, Norway; Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen 5008, Norway; Corresponding authorSummary: Translation initiation is often attributed as the rate-determining step of eukaryotic protein synthesis and key to gene expression control. Despite this centrality, the series of steps involved in this process is poorly understood. Here, we capture the transcriptome-wide occupancy of ribosomes across all stages of translation initiation, enabling us to characterize the transcriptome-wide dynamics of ribosome recruitment to mRNAs, scanning across 5′ UTRs and stop codon recognition, in a higher eukaryote. We provide mechanistic evidence for ribosomes attaching to the mRNA by threading the mRNA through the small subunit. Moreover, we identify features that regulate the recruitment and processivity of scanning ribosomes and redefine optimal initiation contexts. Our approach enables deconvoluting translation initiation into separate stages and identifying regulators at each step. : Giess et al. introduce RCP-seq, a method to study small ribosomal subunit (SSU) dynamics in zebrafish. It reveals threading as the main mode of recruitment to the mRNA and quantifies the impact of sequence features that affect SSU processivity. By contrasting scanning to translating ribosomes, the study calculates initiation rates and redefines the optimal translation initiation context for zebrafish. Keywords: translation, RNA, ribosome profiling, next-generation sequencing, small ribosomal subunit (SSU), scanning processivity, initiation, ribosome recruitment, uORF, Kozak sequencehttp://www.sciencedirect.com/science/article/pii/S2211124720304344 |
| spellingShingle | Adam Giess Yamila N. Torres Cleuren Håkon Tjeldnes Maximilian Krause Teshome Tilahun Bizuayehu Senna Hiensch Aniekan Okon Carston R. Wagner Eivind Valen Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation Cell Reports |
| title | Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation |
| title_full | Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation |
| title_fullStr | Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation |
| title_full_unstemmed | Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation |
| title_short | Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation |
| title_sort | profiling of small ribosomal subunits reveals modes and regulation of translation initiation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720304344 |
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