Selective translational usage of TSS and core promoters revealed by translatome sequencing
Abstract Background In mammals, fine-tuned regulation of gene expression leads to transcription initiation from diverse transcription start sites (TSSs) and multiple core promoters. Although polysome association is a critical step in translation, whether polysome selectively uses TSSs and core promo...
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BMC
2019-04-01
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Series: | BMC Genomics |
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Online Access: | http://link.springer.com/article/10.1186/s12864-019-5650-0 |
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author | Hua Li Ling Bai Hongmei Li Xinhui Li Yani Kang Ningbo Zhang Jielin Sun Zhifeng Shao |
author_facet | Hua Li Ling Bai Hongmei Li Xinhui Li Yani Kang Ningbo Zhang Jielin Sun Zhifeng Shao |
author_sort | Hua Li |
collection | DOAJ |
description | Abstract Background In mammals, fine-tuned regulation of gene expression leads to transcription initiation from diverse transcription start sites (TSSs) and multiple core promoters. Although polysome association is a critical step in translation, whether polysome selectively uses TSSs and core promoters and how this could impact translation remains elusive. Results In this study, we used CAGE followed by deep sequencing to globally profile the transcript 5′ isoforms in the translatome and transcriptome of human HEK293 cells at single-nucleotide resolution. By comparing the two profiles, we identified the 5′ isoforms preferentially used in translatome and revealed a widespread selective usage of TSSs (32.0%) and core promoters (48.7%) by polysome. We discovered the transcription initiation patterns and the sequence characteristics that were highly correlated with polysome selection. We further identified 5804 genes significantly enriched or depleted in translatome and showed that polysome selection was an important contributing factor to the abundance of related gene products. Moreover, after comparison with public transcriptome CAGE data from 180 human tissues and primary cells, we raised a question on whether it is a widely adopted mechanism to regulate translation efficiency by changing the transcription initiation sites on the transcription level in cells of different conditions. Conclusions Using HEK293 cells as a model, we delineated an indirect selection toward TSSs and core promoters by the translation machinery. Our findings lend additional evidence for a much closer coordination between transcription and translation, warranting future translatome studies in more cell types and conditions to develop a more intricate regulatory model for gene expression. |
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institution | Directory Open Access Journal |
issn | 1471-2164 |
language | English |
last_indexed | 2024-12-20T06:49:55Z |
publishDate | 2019-04-01 |
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series | BMC Genomics |
spelling | doaj.art-f719c3e98ff048a7afadc8cbabbaa1722022-12-21T19:49:35ZengBMCBMC Genomics1471-21642019-04-0120111110.1186/s12864-019-5650-0Selective translational usage of TSS and core promoters revealed by translatome sequencingHua Li0Ling Bai1Hongmei Li2Xinhui Li3Yani Kang4Ningbo Zhang5Jielin Sun6Zhifeng Shao7State Key laboratory for Oncogenes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityState Key laboratory for Oncogenes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityInstrumental Analysis Center, Shanghai Jiao Tong UniversityState Key laboratory for Oncogenes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityState Key laboratory for Oncogenes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityKey Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong UniversityState Key laboratory for Oncogenes and Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong UniversityAbstract Background In mammals, fine-tuned regulation of gene expression leads to transcription initiation from diverse transcription start sites (TSSs) and multiple core promoters. Although polysome association is a critical step in translation, whether polysome selectively uses TSSs and core promoters and how this could impact translation remains elusive. Results In this study, we used CAGE followed by deep sequencing to globally profile the transcript 5′ isoforms in the translatome and transcriptome of human HEK293 cells at single-nucleotide resolution. By comparing the two profiles, we identified the 5′ isoforms preferentially used in translatome and revealed a widespread selective usage of TSSs (32.0%) and core promoters (48.7%) by polysome. We discovered the transcription initiation patterns and the sequence characteristics that were highly correlated with polysome selection. We further identified 5804 genes significantly enriched or depleted in translatome and showed that polysome selection was an important contributing factor to the abundance of related gene products. Moreover, after comparison with public transcriptome CAGE data from 180 human tissues and primary cells, we raised a question on whether it is a widely adopted mechanism to regulate translation efficiency by changing the transcription initiation sites on the transcription level in cells of different conditions. Conclusions Using HEK293 cells as a model, we delineated an indirect selection toward TSSs and core promoters by the translation machinery. Our findings lend additional evidence for a much closer coordination between transcription and translation, warranting future translatome studies in more cell types and conditions to develop a more intricate regulatory model for gene expression.http://link.springer.com/article/10.1186/s12864-019-5650-0CAGETranslatome sequencingTSS profilingCore promoterPolysome selection |
spellingShingle | Hua Li Ling Bai Hongmei Li Xinhui Li Yani Kang Ningbo Zhang Jielin Sun Zhifeng Shao Selective translational usage of TSS and core promoters revealed by translatome sequencing BMC Genomics CAGE Translatome sequencing TSS profiling Core promoter Polysome selection |
title | Selective translational usage of TSS and core promoters revealed by translatome sequencing |
title_full | Selective translational usage of TSS and core promoters revealed by translatome sequencing |
title_fullStr | Selective translational usage of TSS and core promoters revealed by translatome sequencing |
title_full_unstemmed | Selective translational usage of TSS and core promoters revealed by translatome sequencing |
title_short | Selective translational usage of TSS and core promoters revealed by translatome sequencing |
title_sort | selective translational usage of tss and core promoters revealed by translatome sequencing |
topic | CAGE Translatome sequencing TSS profiling Core promoter Polysome selection |
url | http://link.springer.com/article/10.1186/s12864-019-5650-0 |
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