{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lewis CJT"],"funding":["American Cancer Society","National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","Pfizer","National Cancer Institute","NCI NIH HHS","National Institutes of Health","National Institute of General Medical Sciences","NIGMS NIH HHS","National Science Foundation"],"pagination":["445-459.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11780321"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["85(2)"],"pubmed_abstract":["mRNA therapeutics offer a potentially universal strategy for the efficient development and delivery of therapeutic proteins. Current mRNA vaccines include chemically modified nucleotides to reduce cellular immunogenicity. Here, we develop an efficient, high-throughput method to measure human translation initiation on therapeutically modified as well as endogenous RNAs. Using systems-level biochemistry, we quantify ribosome recruitment to tens of thousands of human 5' untranslated regions (UTRs) including alternative isoforms and identify sequences that mediate 200-fold effects. We observe widespread effects of coding sequences on translation initiation and identify small regulatory elements of 3-6 nucleotides that are sufficient to potently affect translational output. Incorporation of N1-"],"journal":["Molecular cell"],"pubmed_title":["Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs."],"pmcid":["PMC11780321"],"funding_grant_id":["F31 DK129022","DGE2139841","R01 GM132358","PF-23-1144579-01-RMC","ITEN2021.RNA01","R01 GM101316","R01GM132358","2330451","F31CA254339","F31 CA254339","F31DK129022","R35 GM152167","R35GM152167"],"pubmed_authors":["Thoreen CC","Abdallah K","Gilbert WV","Jin D","Xie LH","Draycott AS","Chen Y","Lewis CJT","Bhandarkar SM"],"additional_accession":[]},"is_claimable":false,"name":"Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs.","description":"mRNA therapeutics offer a potentially universal strategy for the efficient development and delivery of therapeutic proteins. Current mRNA vaccines include chemically modified nucleotides to reduce cellular immunogenicity. Here, we develop an efficient, high-throughput method to measure human translation initiation on therapeutically modified as well as endogenous RNAs. Using systems-level biochemistry, we quantify ribosome recruitment to tens of thousands of human 5' untranslated regions (UTRs) including alternative isoforms and identify sequences that mediate 200-fold effects. We observe widespread effects of coding sequences on translation initiation and identify small regulatory elements of 3-6 nucleotides that are sufficient to potently affect translational output. Incorporation of N1-","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-06T15:23:43.474Z","creation":"2026-06-01T03:11:06.846Z"},"accession":"S-EPMC11780321","cross_references":{"pubmed":["39706187"],"doi":["10.1016/j.molcel.2024.11.030"]}}