Unknown,Transcriptomics,Genomics,Proteomics

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LIN28A-mediated regulation of microRNA biogenesis in mouse embryonic stem cell (A3-1) [Agilent]


ABSTRACT: LIN28A is a highly-conserved RNA-binding protein which is known to be involved in embryonic development, stem cell maintenance and proliferation. LIN28A is expressed in various types of cancer, and they are associated with advanced tumor malignancy. In embryonic stem cell, LIN28A specifically binds to let-7 precursors to suppress biogenesis of the let-7 microRNA family. In addition, LIN28A was reported to bind several mRNAs such as Oct4, cyclin A/B and histone H2A to activate their translation. For comprehensive understanding of the interaction between LIN28A and their target RNAs, we exploited UV-crosslinking and immunoprecipitation (CLIP) to capture their in vivo binding to target RNAs. LIN28A-binding RNAs were identified in a mouse embryonic stem cell line using multiple monoclonal and polyclonal antibodies. The result shows that LIN28 preferentially binds to let-7 precursors through GGAG binding motif, which is consistent with our previous results. We also identified that LIN28A binding is enriched in a certain subset of mRNAs. To understand the function of the novel LIN28A-mRNA binding, we carried out ribosome profiling from LIN28A-depleted mouse embryonic stem cells. Examination of miRNA level in embryonic stem cell treated with siRNA for GFP or for Lin28a

ORGANISM(S): Mus musculus

SUBMITTER: Hyeshik Chang 

PROVIDER: E-GEOD-37112 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

LIN28A is a suppressor of ER-associated translation in embryonic stem cells.

Cho Jun J   Chang Hyeshik H   Kwon S Chul SC   Kim Baekgyu B   Kim Yoosik Y   Choe Junho J   Ha Minju M   Kim Yoon Ki YK   Kim V Narry VN  

Cell 20121025 4


LIN28 plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, LIN28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. In this study, we obtain a genome-wide view of the molecular function of LIN28A in mouse embryonic stem cells by carrying out RNA crosslinking-immunoprecipitation-sequencing (CLIP-seq) and ribosome footprinting. We find that, in addition to let-7 precursors, LIN28A binds to a large  ...[more]

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