Evidence that Lin28 stimulates translation by recruiting RNA helicase A to polysomes.
The stem cell protein Lin28 functions to inhibit the biogenesis of a group of miRNAs but also stimulates the expression of a subset of mRNAs at the post-transcriptional level, the underlying mechanism of which is not yet understood. Here we report the characterization of the molecular interplay between Lin28 and RNA helicase A (RHA) known to play an important role in remodeling ribonucleoprotein particles during translation. We show that reducing Lin28 expression results in decreased RHA association with polysomes while increasing Lin28 expression leads to elevated RHA association. Further, the carboxyl terminus of Lin28 is necessary for interaction with both the amino and carboxyl termini of RHA. Importantly, a carboxyl terminal deletion mutant of Lin28 that retains RNA-binding activity fails to interact with RHA and exhibits dominant-negative effects on Lin28-dependent stimulation of translation. Taken together, these results lead us to suggest that Lin28 may stimulate translation by actively recruiting RHA to polysomes.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Jianyu
J
Jin
Wei
W
Jing
Xin-Xiang
XX
Lei
Chen
C
Feng
Shuping
S
Peng
Kathleen
K
Boris-Lawrie
Yingqun
Y
Huang
D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D011132:Polyribosomes / Q000201:enzymology* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
C000715187:Lin28A protein, human; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C098487:DHX9 protein, human; D053487:DEAD-box RNA Helicases
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