Genomic innovation of ATD alleviates mistranslation associated with multicellularity in Animalia
Abstract
The emergence of multicellularity in Animalia is associated with increase in ROS and expansion of tRNA-isodecoders. tRNA expansion leads to misselection resulting in a critical error of L-Ala mischarged onto tRNAThr, which is proofread by Animalia-specific-tRNA Deacylase (ATD) in vitro. Here we show that in addition to ATD, threonyl-tRNA synthetase (ThrRS) can clear the error in cellular scenario. This two-tier functional redundancy for translation quality control breaks down during oxidative stress, wherein ThrRS is rendered inactive. Therefore, ATD knockout cells display pronounced sensitivity through increased mistranslation of threonine codons leading to cell death. Strikingly, we identify the emergence of ATD along with the error inducing tRNA species starting from Choanoflagellates thus uncovering an important genomic innovation required for multicellularity that occurred in unicellular ancestors of animals. The study further provides a plausible regulatory mechanism wherein the cellular fate of tRNAs can be switched from protein biosynthesis to non-canonical functions.
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Funding
Department of Science and Technology, Ministry of Science and Technology (DST-INSPIRE)
- Santosh Kumar Kuncha
Science and Engineering Research Board (J. C. Bose Fellowship)
- Rajan Sankaranarayanan
Department of Biotechnology , Ministry of Science and Technology (Centre of Excellence)
- Rajan Sankaranarayanan
Council of Scientific and Industrial Research (Healthcare Theme project)
- Rajan Sankaranarayanan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Kuncha et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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