Abstract:
: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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Lin Y,May GE,Kready H,Nazzaro L,Mao M,Spealman P,Creeger Y,McManus CJdoi
10.1093/nar/gkz681subject
Has Abstractpub_date
2019-09-26 00:00:00pages
9358-9367issue
17eissn
0305-1048issn
1362-4962pii
5545010journal_volume
47pub_type
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