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
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Published version
Date
2016-11-23
Authors
Wu, Sen
Mariotti, Marco
Santesmasses, Didac
Hill, Kristina E.
Baclaocos, Janinah
Aparicio-Prat, Estel
Li, Shuping
Mackrill, John
Wu, Yuanyuan
Howard, Michael T.
Journal Title
Journal ISSN
Volume Title
Publisher
The Royal Society
Published Version
Abstract
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.
Description
Keywords
Codon redefinition , Ribosome specialization , Selenocysteine , Selenoprotein P , Selenoprotein S , Genetics , Molecular biology , Cellular biology , Bioinformatics
Citation
Wu, S., Mariotti, M., Santesmasses, D., Hill, K. E., Baclaocos, J., Aparicio-Prat, E., Li, S., Mackrill, J., Wu, Y., Howard, M. T., Capecchi, M., Guigó, R., Burk, R. F. and Atkins, J. F. (2016) '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', Open Biology, 6(11), 160241 (16 pp). doi: 10.1098/rsob.160241