Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements

Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3′ UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site...

ver descrição completa

Detalhes bibliográficos
Autores: Wu, Sen, Mariotti, Marco, 1984-, Santesmasses Ruiz, Didac, 1978-, Hill, Kristina E., Baclaocos, Janinah, Aparicio i Prat, Estel, 1986-, Li, Shuping, Mackrill, John J., Wu, Yuanyuan, Howard, Michael T., Capecchi, Mario, Guigó Serra, Roderic, Burk, Raymond F., Atkins, John F.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/69437
Acesso em linha:http://hdl.handle.net/10230/69437
http://dx.doi.org/10.1098/rsob.160241
Access Level:acceso abierto
Palavra-chave:Codon redefinition
Ribosome specialization
Selenocysteine
Selenoprotein P
Selenoprotein S
Descrição
Resumo:Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3′ UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site just 3′ of SECIS 2, two further sites were identified with one resulting in 10–25% of the mRNA lacking SECIS 2. To address function, mutant mice were generated with either SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon. They were fed on either high or selenium-deficient diets. The mutants had very different effects on the proportions of shorter and longer product Sepp1 protein isoforms isolated from plasma, and on viability. Spatially and functionally distinctive effects of the two SECIS elements on UGA decoding were inferred. We also bioinformatically identify two selenoprotein S mRNAs with different 5′ sequences predicted to yield products with different N-termini. These results provide insights into SECIS function and mRNA processing in selenoprotein isoform diversity.

Registos relacionados