Modulation of the Proteostasis Machinery to  Overcome Stress Caused by Diminished Levels of  t6A-Modified tRNAs in Drosophila

• Published in: Biomolecules (Basel, Switzerland) Vol. 7; no. 1; p. 25
• Main Authors: Rojas-Benítez, Diego, Eggers, Cristián, Glavic, Alvaro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.03.2017; MDPI
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Aggregates; Animals; Cell survival; Codons; Decoding; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Elongation; Fruit flies; Homeostasis; Insects; N6‐threonylcarbamoyladenosine; Protein Biosynthesis; Protein folding; Protein synthesis; Proteins; RNA Processing, Post-Transcriptional; RNA, Transfer - metabolism; Structural stability; Transcription; Translation initiation; tRNA; tRNA post‐transcriptional modification; Unfolded Protein Response; unfolded protein response; unfolded protein response; tRNA post‐transcriptional modification; N6‐threonylcarbamoyladenosine
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom7010025

Transfer RNAs (tRNAs) harbor a subset of post-transcriptional modifications required for structural stability or decoding function. N6-threonylcarbamoyladenosine (t6A) is a universally conserved modification found at position 37 in tRNA that pair A-starting codons (ANN) and is required for proper translation initiation and to prevent frame shift during elongation. In its absence, the synthesis of aberrant proteins is likely, evidenced by the formation of protein aggregates. In this work, our aim was to study the relationship between t6A-modified tRNAs and protein synthesis homeostasis machinery using Drosophila melanogaster. We used the Gal4/UAS system to knockdown genes required for t6A synthesis in a tissue and time specific manner and in vivo reporters of unfolded protein response (UPR) activation. Our results suggest that t6A-modified tRNAs, synthetized by the threonyl-carbamoyl transferase complex (TCTC), are required for organismal growth and imaginal cell survival, and is most likely to support proper protein synthesis.