Inhibition of specific gene expressions by protein-mediated mRNA interference.
RNA interference mediated by RNA such as antisense RNA, short interfering RNA and micro RNA is well documented to regulate specific gene expression at the level of messenger RNA. However, RNA interference mediated by proteins has not been reported. Here we identify the MazF-hw mRNA interferase from a superhalophilic archaeon that cleaves RNA at a specific seven-base sequence (UUACUCA). This sequence was found unusually abundant in the mRNAs for rhodopsin transcription activator and some membrane proteins of the archaeon, suggesting that the expression of these proteins is regulated by MazF-hw. When all of the seven-base cleavage sites in essential genes in Escherichia coli were eliminated, the cells were no longer sensitive to MazF-hw, demonstrating that specific gene expression can be regulated by a sequence-specific mRNA interferase. These findings demonstrate that mRNA interference can be mediated not only by RNA but also by proteins to effectively silence specific gene expression in cells.
Department of Biochemistry, Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Yoshihiro
Y
Yamaguchi
Hirofumi
H
Nariya
Jung-Ho
JH
Park
Masayori
M
Inouye
D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D019605:Euryarchaeota / Q000235:genetics; D020869:Gene Expression Profiling; D020868:Gene Silencing; D008957:Models, Genetic; D008969:Molecular Sequence Data; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422955:MazF protein, E coli; D012333:RNA, Messenger; D012243:Rhodopsin; D004722:Endoribonucleases