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Mol Cell DOI:10.1016/j.molcel.2012.04.008

Reduced expression of ribosomal proteins relieves microRNA-mediated repression.

Publication TypeJournal Article
Year of Publication2012
AuthorsJanas, MM, Wang, E, Love, T, Harris, AS, Stevenson, K, Semmelmann, K, Shaffer, JM, Chen, P-H, Doench, JG, Yerramilli, SVBK, Neuberg, DS, Iliopoulos, D, Housman, DE, Burge, CB, Novina, CD
JournalMol Cell
Date Published2012 Apr 27
KeywordsHeLa Cells, Humans, MicroRNAs, Peptide Chain Initiation, Translational, Ribosomal Proteins, RNA Interference, Tumor Suppressor Protein p53

MicroRNAs (miRNAs) regulate physiological and pathological processes by inducing posttranscriptional repression of target messenger RNAs (mRNAs) via incompletely understood mechanisms. To discover factors required for human miRNA activity, we performed an RNAi screen using a reporter cell line of miRNA-mediated repression of translation initiation. We report that reduced expression of ribosomal protein genes (RPGs) dissociated miRNA complexes from target mRNAs, leading to increased polysome association, translation, and stability of miRNA-targeted mRNAs relative to untargeted mRNAs. RNA sequencing of polysomes indicated substantial overlap in sets of genes exhibiting increased or decreased polysomal association after Argonaute or RPG knockdowns, suggesting similarity in affected pathways. miRNA profiling of monosomes and polysomes demonstrated that miRNAs cosediment with ribosomes. RPG knockdowns decreased miRNAs in monosomes and increased their target mRNAs in polysomes. Our data show that most miRNAs repress translation and that the levels of RPGs modulate miRNA-mediated repression of translation initiation.


Alternate JournalMol. Cell
PubMed ID22541556