{"messages":[{"status":"ok","category":"all"}], "collection":[{"title":"Decoding mRNA translatability and stability from 5'UTR","authors":"Jia, L.; Mao, Y.; Ji, Q.; Dersh, D.; Yewdell, J. W.; Qian, S.-B.","author_corresponding":"Shu-Bing  Qian","author_corresponding_institution":"Cornell University","doi":"10.1101\/2020.03.13.990887","date":"2020-03-15","version":"1","type":"new results","license":"cc_by_nd","category":"biochemistry","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2020\/03\/15\/2020.03.13.990887.source.xml","abstract":"Precise control of protein synthesis by engineering sequence elements in 5 untranslated region (5UTR) remains a fundamental challenge. To accelerate our understanding of cis-regulatory code embedded in 5UTR, we devised massively parallel reporter assays from a synthetic mRNA library composed of over one million 5UTR variants. A completely randomized 10-nucleotide sequence preceding an upstream open reading frame (uORF) and downstream GFP leads to a broad range of mRNA translatability and stability in mammalian cells. While efficient translation protects mRNA from degradation, uORF translation triggers mRNA decay in a UPF1-dependent manner. We also identified translational inhibitory elements in 5UTR with G-quadruplex as a mark for mRNA decay in the P-body. Unexpectedly, an unstructured A-rich element in 5UTR, while enabling cap-independent translation, destabilizes mRNAs in the absence of translation. Our results not only expose diverse sequence features of 5UTR in controlling mRNA translatability, but also reveal ribosome-dependent and -independent mRNA surveillance pathways.","funder":"NA","published":"10.1038\/s41594-020-0465-x","server":"bioRxiv"}]}