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Functional characterization of alternatively spliced human SECISBP2 transcript variants
Nucleic Acids Research (2008)
  • Laura V. Papp, Queensland Institute of Medical Research
  • Junning Wang, University of Massachusetts Medical School Worcester
  • Derek Kennedy, Griffith University
  • Didier Boucher, Queensland Institute of Medical Research
  • Yan Zhang, University of Nebraska - Lincoln
  • Vadim N. Gladyshev, University of Nebraska - Lincoln
  • Ravindra N. Singh, University of Massachusetts Medical School Worcester
  • Kum Kum Khanna, Queensland Institute of Medical Research
Abstract
Synthesis of selenoproteins depends on decoding of
the UGA stop codon as the amino acid selenocysteine
(Sec). This process requires the presence of
a Sec insertion sequence element (SECIS) in the
3’-untranslated region of selenoprotein mRNAs and
its interaction with the SECIS binding protein 2
(SBP2). In humans, mutations in the SBP2-encoding
gene Sec insertion sequence binding protein 2
(SECISBP2) that alter the amino acid sequence
or cause splicing defects lead to abnormal thyroid
hormone metabolism. Herein, we present the first
in silico and in vivo functional characterization
of alternative splicing of SECISBP2. We report a
complex splicing pattern in the 5’-region of human
SECISBP2, wherein at least eight splice variants
encode five isoforms with varying N-terminal
sequence. One of the isoforms, mtSBP2, contains a
mitochondrial targeting sequence and localizes to
mitochondria. Using a minigene-based in vivo splicing
assay we characterized the splicing efficiency
of several alternative transcripts, and show that the
splicing event that creates mtSBP2 can be modulated
by antisense oligonucleotides. Moreover, we
show that full-length SBP2 and some alternatively
spliced variants are subject to a coordinated transcriptional
and translational regulation in response
to ultraviolet type A irradiation-induced stress.
Overall, our data broadens the functional scope of
a housekeeping protein essential to selenium
metabolism.
Publication Date
2008
DOI
10.1093/nar/gkn829
Publisher Statement
This is an article from Nucleic Acids Research 36 (2008): 7192, doi:10.1093/nar/gkn829
Posted with permission. Copyright 2008 The Authors
Citation Information
Laura V. Papp, Junning Wang, Derek Kennedy, Didier Boucher, et al.. "Functional characterization of alternatively spliced human SECISBP2 transcript variants" Nucleic Acids Research Vol. 36 Iss. 22 (2008) p. 7192 - 7206
Available at: http://works.bepress.com/ravindra-singh/13/
Creative Commons license
Creative Commons License
This work is licensed under a Creative Commons CC_BY-NC International License.