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Publication : Determinants of mRNA recognition and translation regulation by Lin28.

First Author  Lei XX Year  2012
Journal  Nucleic Acids Res Volume  40
Issue  8 Pages  3574-84
PubMed ID  22210884 Mgi Jnum  J:197730
Mgi Id  MGI:5494384 Doi  10.1093/nar/gkr1279
Citation  Lei XX, et al. (2012) Determinants of mRNA recognition and translation regulation by Lin28. Nucleic Acids Res 40(8):3574-84
abstractText  Lin28 is critical for stem cell maintenance and is also associated with advanced human malignancies. Our recent genome-wide studies mark Lin28 as a master post-transcriptional regulator of a subset of messenger RNAs important for cell growth and metabolism. However, the molecular basis underpinning the selective mRNA target regulation is unclear. Here, we provide evidence that Lin28 recognizes a unique motif in multiple target mRNAs, characterized by a small but critical 'A' bulge flanked by two G:C base pairs embedded in a complex secondary structure. This motif mediates Lin28-dependent stimulation of translation. As Lin28 is also known to inhibit the biogenesis of a cohort of miRNAs including let-7, we propose that Lin28 binding to different RNA types (precursor miRNAs versus mRNAs) may facilitate recruitment of different co-factors, leading to distinct regulatory outcomes. Our findings uncover a putative yet unexpected motif that may constitute a mechanistic base for the multitude of functions regulated by Lin28 in both stem cells and cancer cells.
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