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Transcriptome-Wide Profiling of Protein-RNA Interactions by Cross-Linking and Immunoprecipitation Mediated by FLAG-Biotin Tandem Purification
Published on: May 18, 2020
A mirror of two faces: Lin28 as a master regulator of both miRNA and mRNA
1Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA. yingqun.huang@yale.edu
Abstract:
Lin28 is an evolutionarily conserved RNA-binding protein that plays important roles in development, pluripotency, tumorigenesis, and metabolism. Emerging evidence suggests that the pleiotropic roles of Lin28 in the diverse physiological and pathological processes are mechanistically linked to its ability to modulate not only the biogenesis of miRNAs, particularly the let-7 family miRNAs, but also the translation of mRNAs important for cell growth and metabolism. Let-7 negatively regulates the translation of oncogenes, cell cycle regulators, and metabolic pathway components. Lin28 relieves this repression by blocking the production of mature let-7. Lin28 binds to the terminal loops of let-7 precursors, leading to inhibition of processing and the induction of uridylation and precursor degradation. Lin28 also is a direct translational regulator: it selectively binds to a cohort of mRNAs and stimulates their translation. Recent advances in our understanding of Lin28-mediated mechanisms of posttranscriptional regulation of gene expression reveal important roles of this protein in the fields of development, stem cells, metabolic diseases, and cancer.
Insights
Lin28 protein regulates gene expression by controlling microRNA (miRNA) production and messenger RNA (mRNA) translation. It impacts development, stem cells, metabolism, and cancer by modulating the let-7 miRNA family.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cancer Biology
Background:
- Lin28 is an evolutionarily conserved RNA-binding protein.
- It plays critical roles in development, pluripotency, tumorigenesis, and metabolism.
- Lin28's functions are linked to its modulation of miRNA biogenesis and mRNA translation.
Purpose of the Study:
- To elucidate the mechanisms by which Lin28 regulates gene expression.
- To understand Lin28's role in cellular processes like development and disease.
- To highlight recent advances in Lin28-mediated posttranscriptional regulation.
Main Methods:
- Investigating Lin28's interaction with let-7 precursor miRNAs.
- Analyzing Lin28's effect on miRNA processing and degradation.
- Studying Lin28's direct binding to mRNAs and its impact on translation.
Main Results:
- Lin28 inhibits the maturation of let-7 miRNAs by binding to their precursors, promoting uridylation and degradation.
- Lin28 selectively binds to specific mRNAs, thereby stimulating their translation.
- These actions collectively influence cell growth, metabolism, and oncogenesis.
Conclusions:
- Lin28 acts as a crucial posttranscriptional regulator of gene expression.
- Its mechanisms involve both miRNA biogenesis inhibition and direct mRNA translational control.
- Understanding Lin28 is vital for research in development, stem cells, metabolic diseases, and cancer.
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