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. |