Decoding apparatus for eukaryotic selenocysteine insertion.
Decoding UGA as selenocysteine requires a unique tRNA, a specialized elongation factor, and specific secondary structures in the mRNA, termed SECIS elements. Eukaryotic SECIS elements are found in the 3' untranslated region of selenoprotein mRNAs while those in prokaryotes occur immediately downstream of UGA. Consequently, a single eukaryotic SECIS element can serve multiple UGA codons, whereas prokaryotic SECIS elements only function for the adjacent UGA, suggesting distinct mechanisms for recoding in the two kingdoms. We have identified and characterized the first eukaryotic selenocysteyl-tRNA-specific elongation factor. This factor forms a complex with mammalian SECIS binding protein 2, and these two components function together in selenocysteine incorporation in mammalian cells. Expression of the two functional domains of the bacterial elongation factor-SECIS binding protein as two separate proteins in eukaryotes suggests a mechanism for rapid exchange of charged for uncharged selenocysteyl-tRNA-elongation factor complex, allowing a single SECIS element to serve multiple UGA codons.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
R M
RM
Tujebajeva
P R
PR
Copeland
X M
XM
Xu
B A
BA
Carlson
J W
JW
Harney
D M
DM
Driscoll
D L
DL
Hatfield
M J
MJ
Berry
D020413:3' Untranslated Regions / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D017279:Selenocysteine / Q000235:genetics* / Q000378:metabolism; D051140:Selenoproteins; D016415:Sequence Alignment; D014162:Transfection
D020413:3' Untranslated Regions; D010445:Peptide Elongation Factors; D011506:Proteins; D012346:RNA, Transfer, Amino Acyl; D016601:RNA-Binding Proteins; C121530:SECISBP2 protein, human; C498488:Secisbp2 protein, rat; D051140:Selenoproteins; C112705:selenocysteinyl-tRNA; D017279:Selenocysteine