Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells.
Lin28 acts as a repressor of microRNA processing and as a post-transcriptional regulatory factor for a subset of mRNAs. Here we report that in human embryonic stem cells Lin28 facilitates the expression of the pivotal pluripotency factor Oct4 at the post-transcriptional level. We provide evidence that Lin28 binds Oct4 mRNA directly through high affinity sites within its coding region and that an interaction between Lin28 and RNA helicase A (RHA) may play a part in the observed regulation. We further demonstrate that decreasing RHA levels impairs Lin28-dependent stimulation of translation in a reporter system. Taken together with previous studies showing that RHA is required for efficient translation of a specific class of mRNAs, these findings suggest a novel mechanism by which Lin28 may affect target mRNA expression and represent the first evidence of post-transcriptional regulation of Oct4 expression by Lin28 in human embryonic stem cells.
Qiu
Caihong
C
Yale Stem Cell Center, PO Box 208073, New Haven, CT 06520, USA.
Ma
Yinghong
Y
Wang
Jianquan
J
Peng
Shuping
S
Huang
Yingqun
Y
D001665:Binding Sites; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C000715187:Lin28A protein, human; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases