title: RNA-binding protein HuD controls insulin translation.
abstract: Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic β cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic β cells.
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Wook
authors.initials: W
authors.lastname: Kim
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tominaga
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Subaran
authors.forename: Olga D
authors.initials: OD
authors.lastname: Carlson
authors.forename: Evi M
authors.initials: EM
authors.lastname: Mercken
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Nora I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D000067779:ELAV-Like Protein 4; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; C498011:Elavl4 protein, mouse; C561967:Ins2 protein, mouse; D007328:Insulin; D011498:Protein Precursors; C013737:preproinsulin; D005947:Glucose