miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1.
These studies show that miR-122, a 22-nucleotide microRNA, is derived from a liver-specific noncoding polyadenylated RNA transcribed from the gene hcr. The exact sequence of miR-122 as well as the adjacent secondary structure within the hcr mRNA are conserved from mammalian species back to fish. Levels of miR-122 in the mouse liver increase to half maximal values around day 17 of embryogenesis, and reach near maximal levels of 50,000 copies per average cell before birth. Lewis et al. (2003) predicted the cationic amino acid transporter (CAT-1 or SLC7A1) as a miR-122 target. CAT-1 protein and its mRNA are expressed in all mammalian tissues but with lower levels in adult liver. Furthermore, during mouse liver development CAT-1 mRNA decreases in an almost inverse correlation with miR-122. Eight potential miR-122 target sites were predicted within the human CAT-1 mRNA, with six in the 3'-untranslated region. Using a reporter construct it was found that just three of the predicted sites, linked in a 400-nucleotide sequence from human CAT-1, acted with synergy and were sufficient to strongly inhibit protein synthesis and reduce mRNA levels. In summary, these studies followed the accumulation during development of miR-122 from its mRNA precursor, hcr, through to identification of what may be a specific mRNA target, CAT-1.
Chang
Jinhong
J
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497, USA.
Nicolas
Emmanuelle
E
Marks
Debora
D
Sander
Chris
C
Lerro
Anthony
A
Buendia
Marie Annick
MA
Xu
Chunxiao
C
Mason
William S
WS
Moloshok
Thomas
T
Bort
Roque
R
Zaret
Kenneth S
KS
Taylor
John M
JM
D000818:Animals; D027201:Cationic Amino Acid Transporter 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism* / Q000502:physiology; D026723:Polyadenylation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism
C412616:CCHCR1 protein, human; D027201:Cationic Amino Acid Transporter 1; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; C420825:SLC7A1 protein, human