Stop codon suppression via inhibition of eRF1 expression.
In humans, recognition of a stop codon by protein release factor eRF1 leads to release of the nascent peptide from the ribosome. Although efficient eRF1 activity is usually desirable, numerous pathologies result from eRF1 recognition of premature stop mutations in essential genes. In these cases, decreased eRF1 activity could increase readthrough of the premature stop codon, thereby making full-length protein. To broaden the means available to beneficially decrease eRF1 activity, we have targeted eRF1 mRNA using siRNAs and antisense oligonucleotides. We show that both eRF1-targeted siRNA and antisense oligonucleotides decrease eRF1 mRNA and eRF1 protein concentrations, and increase UAG readthrough in cultured human cells.
Carnes
Jason
J
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309-0347, USA.
Jacobson
Marty
M
Leinwand
Leslie
L
Yarus
Michael
M
D001483:Base Sequence; D002460:Cell Line; D018388:Codon, Terminator; D005786:Gene Expression Regulation; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010441:Peptide Chain Elongation, Translational; D010454:Peptide Termination Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
D018388:Codon, Terminator; C489002:ETF1 protein, human; D016376:Oligonucleotides, Antisense; D010454:Peptide Termination Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering