10.1184/R1/10110866.v1
Yizhu Lin
Yizhu
Lin
Gemma May
Gemma
May
Hunter Kready
Hunter
Kready
Lauren Nazzaro
Lauren
Nazzaro
Mao Mao
Mao
Mao
Pieter Spealman
Pieter
Spealman
Yehuda Creeger
Yehuda
Creeger
C. Joel McManus
C. Joel
McManus
Impacts of uORF codon identity and position on translation regulation
Carnegie Mellon University
2019
RNA characterization
RNA manipulation
RNA protein complex
2019-10-31 16:37:27
Journal contribution
https://kilthub.cmu.edu/articles/journal_contribution/Impacts_of_uORF_codon_identity_and_position_on_translation_regulation/10110866
Translation regulation plays an important role in eukaryotic gene expression. Upstream open reading frames (uORFs) are potent regulatory elements located in 5′ mRNA transcript leaders. Translation of uORFs usually inhibit the translation of downstream main open reading frames, but some enhance expression. While a minority of uORFs encode conserved functional peptides, the coding regions of most uORFs are not conserved. Thus, the importance of uORF coding sequences on their regulatory functions remains largely unknown. We investigated the impact of an uORF coding region on gene regulation by assaying the functions of thousands of variants in the yeast YAP1 uORF. Varying uORF codons resulted in a wide range of functions, including repressing and enhancing expression of the downstream ORF. The presence of rare codons resulted in the most inhibitory YAP1 uORF variants. Inhibitory functions of such uORFs were abrogated by overexpression of complementary tRNA. Finally, regression analysis of our results indicated that both codon identity and position impact uORF function. Our results support a model in which a uORF coding sequence impacts its regulatory functions by altering the speed of uORF translation.