Generally applicable transcriptome-wide analysis of translation using anota2seq
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Abstract
mRNA translation plays an evolutionarily conserved role in homeostasis and when dysregulated contributes to various disorders including metabolic and neurological diseases and cancer. Notwithstanding that optimal and universally applicable methods are critical for understanding the complex role of translational control under physiological and pathological conditions, approaches to analyze translatomes are largely underdeveloped. To address this, we developed the anota2seq algorithm which outperforms current methods for statistical identification of changes in translation. Notably, in contrast to available analytical methods, anota2seq also allows specific identification of an underappreciated mode of gene expression regulation whereby translation acts as a buffering mechanism which maintains protein levels despite fluctuations in corresponding mRNA abundance (‘translational buffering’). Thus, the universal anota2seq algorithm allows efficient and hitherto unprecedented interrogation of translatomes which is anticipated to advance knowledge regarding the role of translation in homeostasis and disease.
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Self-citation
- Authors
- Oertlin, C., Lorent, J., Murie, C., Furic, L., Topisirovic, I., & Larsson, O.
- Affiliations
- Science for Life Laboratory (SE)
- The University of Melbourne (AU)
- Lady Davis Institute, SMBD Jewish General Hospital, Gerald Bronfman Department of Oncology, and Departments of Experimental Medicine, and Biochemistry McGill University, Montreal, Canada
- Corresponding author
- Larsson, Ola
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-03-30
- Volume
- 47
- Issue
- 12
- Pages
- e70-e70
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC6614820
- OpenAlex
- W2932166412
- Cited by
- 107
- References
- 12
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 10 · 2023: 10 · 2022: 16 · 2021: 18 · 2020: 13 · 2019: 10 · 2018: 4
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Funders
- Swedish Research Council
- Swedish Cancer Society
- Cancer Society in Stockholm
- Wallenberg Academy Fellows Program
- Canadian Institutes for Health Research (MOP-363027)
- National Institutes of Health (R01 CA 202021-01-A1)
- Fonds de Recherche du Québec – Santé (FRQ-S)
- Joint Canada-Israel Health Research Program (108589-001)
- Victorian Cancer Agency (MCRF16007)
- National Health and Medical Research Council (APP1141339)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- mRNA translation, translatome, translational regulation, protein abundance, mRNA levels, gene expression regulation, algorithm development
- MeSH terms
- Algorithms, Data Interpretation, Statistical, Proteins, Ribosomal Proteins, Ribosomes, Protein Biosynthesis, Sequence Analysis, RNA, Oligonucleotide Array Sequence Analysis, Transcriptome
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