Adaptation of codon usage to tRNA I34 modification controls translation kinetics and proteome landscape

Autoři: Xueliang Lyu aff001;  Qian Yang aff002;  Lin Li aff003;  Yunkun Dang aff004;  Zhipeng Zhou aff002;  She Chen aff002;  Yi Liu aff002
Působiště autorů: State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China aff001;  Department of Physiology, The University of Texas Southwestern Medical Center,Harry Hines Blvd., Dallas, Texas, United States of America aff002;  National Institute of Biological Sciences, Changping District, Beijing, China aff003;  State Key Laboratory for Conservation and Utilization of Bio-Resources and Center for Life Science, School of Life Sciences, Yunnan University, Kunming, China aff004;  College of Life Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei, China aff005
Vyšlo v časopise: Adaptation of codon usage to tRNA I34 modification controls translation kinetics and proteome landscape. PLoS Genet 16(6): e1008836. doi:10.1371/journal.pgen.1008836
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008836


Codon usage bias is a universal feature of all genomes and plays an important role in regulating protein expression levels. Modification of adenosine to inosine at the tRNA anticodon wobble position (I34) by adenosine deaminases (ADATs) is observed in all eukaryotes and has been proposed to explain the correlation between codon usage and tRNA pool. However, how the tRNA pool is affected by I34 modification to influence codon usage-dependent gene expression is unclear. Using Neurospora crassa as a model system, by combining molecular, biochemical and bioinformatics analyses, we show that silencing of adat2 expression severely impaired the I34 modification levels for the ADAT-related tRNAs, resulting in major ADAT-related tRNA profile changes and reprogramming of translation elongation kinetics on ADAT-related codons. adat2 silencing also caused genome-wide codon usage-biased ribosome pausing on mRNAs and proteome landscape changes, leading to selective translational repression or induction of different mRNAs. The induced expression of CPC-1, the Neurospora ortholog of yeast GCN4p, mediates the transcriptional response after adat2 silencing and amino acid starvation. Together, our results demonstrate that the tRNA I34 modification by ADAT plays a major role in driving codon usage-biased translation to shape proteome landscape.

Klíčová slova:

Anticodons – Eukaryota – Gene expression – Messenger RNA – Neurospora – Protein translation – Ribosomes – Transfer RNA


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