Abstract

MicroRNAs are small noncoding RNAs thought to have pivotal roles in numerous diseases and developmental processes. However, a growing body of literature indicates that in vivo elimination of these tiny RNAs usually has little to no observable consequence, suggesting functional redundancy with other microRNAs or cellular pathways. We provide an in-depth analysis of miR-205 expression and define miR-205 as an epithelial-specific microRNA, and for the first time show that ablation of this microRNA knockout exhibits partially penetrant lethality in a constitutive mouse knockout model. Given the role of this microRNA in cancer and development, this mouse model will be an incredible reagent to study the function and mechanisms of miR-205 in epithelial tissue development and disease.

Highlights

  • Noncoding RNAs are recognized as key components of gene regulation

  • A growing body of literature suggests that elimination of both single miRNAs and miRNA families has little to no observable consequence in unstressed conditions [7,8]

  • KO animals were born normal, they exhibited a weight decrease by postnatal day 7 and a partially penetrant postnatal lethality by postnatal day 14. These data reveal an important role for miR-205 in stratified squamous epithelial-derived tissues, providing an in vivo model for further understanding the roles of a noncoding RNA in basic physiology and potentially in the context of human disease

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Summary

Introduction

Noncoding RNAs are recognized as key components of gene regulation. While the classes of noncoding RNAs are a growing list, microRNAs (miRNAs) are among the most characterized. miRNAs are small, ,22 nt RNAs that function to negatively regulate gene expression by targeting complementary mRNAs [1]. While little in vivo data is available for miR-205, the tumor protein p63 has been found to regulate its expression and is essential for mouse development and proper squamous epithelium differentiation and maintenance [19,20]. These data reveal an important role for miR-205 in stratified squamous epithelial-derived tissues, providing an in vivo model for further understanding the roles of a noncoding RNA in basic physiology and potentially in the context of human disease.

Results
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