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XB-ART-40604
Development. December 1, 2009; 136 (23): 3927-36.

The miR-30 miRNA family regulates Xenopus pronephros development and targets the transcription factor Xlim1/Lhx1.



Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They are involved in diverse biological processes, such as development, differentiation, cell proliferation and apoptosis. To study the role of miRNAs during pronephric kidney development of Xenopus, global miRNA biogenesis was eliminated by knockdown of two key components: Dicer and Dgcr8. These embryos developed a range of kidney defects, including edema formation, delayed renal epithelial differentiation and abnormal patterning. To identify a causative miRNA, mouse and frog kidneys were screened for putative candidates. Among these, the miR-30 family showed the most prominent kidney-restricted expression. Moreover, knockdown of miR-30a-5p phenocopied most of the pronephric defects observed upon global inhibition of miRNA biogenesis. Molecular analyses revealed that miR-30 regulates the LIM-class homeobox factor Xlim1/Lhx1, a major transcriptional regulator of kidney development. miR-30 targeted Xlim1/Lhx1 via two previously unrecognized binding sites in its 3''UTR and thereby restricted its activity. During kidney development, Xlim1/Lhx1 is required in the early stages, but is downregulated subsequently. However, in the absence of miR-30 activity, Xlim1/Lhx1 is maintained at high levels and, therefore, may contribute to the delayed terminal differentiation of the amphibian pronephros.

PubMed ID: 19906860
PMC ID: PMC2778741
Article link: Development.
Grant support: #5R21DK077763-03 NIDDK NIH HHS , R21 DK077763-02 NIDDK NIH HHS , R01 DK080745 NIDDK NIH HHS , R21 DK077763 NIDDK NIH HHS , R01 DK080745 NIDDK NIH HHS , R21 DK077763 NIDDK NIH HHS , R21 DK077763-02 NIDDK NIH HHS , #5R21DK077763-03 NIDDK NIH HHS

Genes referenced: atp1a1 atp1b1 cad cald1 cdh16 clcnkb dgcr8 dicer1 hnf1a lhx1 nfyc pax2 pax8 slc12a1 slc12a3 slc5a1.2 sult2a1 tbx2

Morpholinos referenced: dgcr8 MO1 dicer1 MO5 nfyc MO1

References:
Abbott, 2005, Pubmed[+]


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