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Determinants of mRNA recognition and translation regulation by Lin28

Xin-Xiang Lei1, Jie Xu, Wei Ma

  • 1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA.

Nucleic Acids Research
|January 3, 2012
PubMed

Insights

Lin28 protein regulates gene expression by binding a specific RNA motif, impacting stem cells and cancer. This discovery reveals how Lin28 controls cell growth and metabolism through selective messenger RNA targeting.

Area of Science:

  • Molecular Biology
  • Stem Cell Biology
  • Cancer Research

Background:

  • Lin28 is crucial for maintaining stem cell pluripotency.
  • Lin28 is implicated in the progression of human cancers.
  • Lin28 acts as a master regulator of post-transcriptional gene expression for specific mRNAs involved in cell growth and metabolism.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Lin28 selectively binds and regulates target mRNAs.
  • To identify the specific RNA motif recognized by Lin28.
  • To understand how Lin28's regulatory outcomes differ between messenger RNAs and microRNAs.

Main Methods:

  • Genome-wide studies to identify Lin28 targets.
  • RNA structure analysis to characterize the binding motif.
  • Functional assays to assess Lin28-mediated translational control.

Main Results:

  • Identified a unique RNA motif recognized by Lin28, featuring an 'A' bulge flanked by G:C base pairs within a complex secondary structure.
  • Demonstrated that this motif mediates Lin28-dependent stimulation of translation for target mRNAs.
  • Proposed a model where Lin28 recruits distinct co-factors for regulating precursor microRNAs (like let-7) versus messenger RNAs, leading to varied outcomes.

Conclusions:

  • Lin28 utilizes a specific RNA motif for selective mRNA targeting and translational control.
  • This motif provides a mechanistic basis for Lin28's diverse roles in stem cell maintenance and cancer.
  • Understanding Lin28-RNA interactions offers insights into therapeutic strategies for stem cell-related disorders and malignancies.

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