Detecting translational regulation by change point analysis of ribosome profiling data sets
© 2014 Zupanic et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society..
Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While during normal translation, ribosome density is constant along the length of the mRNA coding region, this can be altered in response to translational regulatory events. In the present study, we developed a method to detect translational regulation of individual mRNAs from their ribosome profiles, utilizing changes in ribosome density. We used mathematical modeling to show that changes in ribosome density should occur along the mRNA at the point of regulation. We analyzed a Ribo-Seq data set obtained for mouse embryonic stem cells and showed that normalization by corresponding RNA-Seq can be used to improve the Ribo-Seq quality by removing bias introduced by deep-sequencing and alignment artifacts. After normalization, we applied a change point algorithm to detect changes in ribosome density present in individual mRNA ribosome profiles. Additional sequence and gene isoform information obtained from the UCSC Genome Browser allowed us to further categorize the detected changes into different mechanisms of regulation. In particular, we detected several mRNAs with known post-transcriptional regulation, e.g., premature termination for selenoprotein mRNAs and translational control of Atf4, but also several more mRNAs with hitherto unknown translational regulation. Additionally, our approach proved useful for identification of new transcript isoforms.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2014 |
|---|---|
| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
|---|---|
| Enthalten in: |
RNA (New York, N.Y.) - 20(2014), 10 vom: 15. Okt., Seite 1507-18 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zupanic, Anze [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Change point analysis |
|---|
| Anmerkungen: |
Date Completed 29.01.2015 Date Revised 29.01.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1261/rna.045286.114 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM241204488 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM241204488 | ||
| 003 | DE-627 | ||
| 005 | 20231224123738.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1261/rna.045286.114 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0804.xml |
| 035 | |a (DE-627)NLM241204488 | ||
| 035 | |a (NLM)25147239 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zupanic, Anze |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Detecting translational regulation by change point analysis of ribosome profiling data sets |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.01.2015 | ||
| 500 | |a Date Revised 29.01.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2014 Zupanic et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. | ||
| 520 | |a Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While during normal translation, ribosome density is constant along the length of the mRNA coding region, this can be altered in response to translational regulatory events. In the present study, we developed a method to detect translational regulation of individual mRNAs from their ribosome profiles, utilizing changes in ribosome density. We used mathematical modeling to show that changes in ribosome density should occur along the mRNA at the point of regulation. We analyzed a Ribo-Seq data set obtained for mouse embryonic stem cells and showed that normalization by corresponding RNA-Seq can be used to improve the Ribo-Seq quality by removing bias introduced by deep-sequencing and alignment artifacts. After normalization, we applied a change point algorithm to detect changes in ribosome density present in individual mRNA ribosome profiles. Additional sequence and gene isoform information obtained from the UCSC Genome Browser allowed us to further categorize the detected changes into different mechanisms of regulation. In particular, we detected several mRNAs with known post-transcriptional regulation, e.g., premature termination for selenoprotein mRNAs and translational control of Atf4, but also several more mRNAs with hitherto unknown translational regulation. Additionally, our approach proved useful for identification of new transcript isoforms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a change point analysis | |
| 650 | 4 | |a mathematical modeling | |
| 650 | 4 | |a ribosome profiling | |
| 650 | 4 | |a translation regulation | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Meplan, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Grellscheid, Sushma N |e verfasserin |4 aut | |
| 700 | 1 | |a Mathers, John C |e verfasserin |4 aut | |
| 700 | 1 | |a Kirkwood, Tom B L |e verfasserin |4 aut | |
| 700 | 1 | |a Hesketh, John E |e verfasserin |4 aut | |
| 700 | 1 | |a Shanley, Daryl P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t RNA (New York, N.Y.) |d 1995 |g 20(2014), 10 vom: 15. Okt., Seite 1507-18 |w (DE-627)NLM074661159 |x 1469-9001 |7 nnns |
| 773 | 1 | 8 | |g volume:20 |g year:2014 |g number:10 |g day:15 |g month:10 |g pages:1507-18 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1261/rna.045286.114 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 20 |j 2014 |e 10 |b 15 |c 10 |h 1507-18 | ||