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 3ЈUTR 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.

MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney

“…We have previously demonstrated that the loss of miRNAs in early Xenopus development resulted in a range of pronephric kidney phenotypes (11). We further determined that part of the kidney phenotype was due to the loss of miR-30 miRNA family expression and the ensuing up-regulation of Lhx1, a key transcription factor in kidney development.…”

“…Antisense morpholino oligomers were diluted to a concentration of 1 mM. The xDicer-MO and Pten-MO have been previously published (11,36). The Ins-MO and Igf2-MO were tested using GFP fusion protein constructs (Fig.…”

“…In our previous study on the role of microRNAs (miRNAs) during Xenopus development, we observed that inhibiting miRNA biogenesis causes a reduction in the size of the pronephric kidney (11). miRNAs are small noncoding RNA molecules that regulate gene expression at the posttranscriptional level by binding to the 3′ UTR of target mRNAs (12).…”

Circulating MicroRNA‐188, ‐30a, and ‐30e as Early Biomarkers for Contrast‐Induced Acute Kidney Injury

“…MiRNA‐30a and miRNA‐30e, members of the miRNA‐30 family, are functionally related to each other. They play important roles in renal development and maintaining renal function 25. However, the levels of miRNA‐30a and miRNA‐30e did not show significant change in kidney samples from CI‐AKI rats.…”

Expression profile analysis of microRNAs and downregulated miR-486-5p and miR-30a-5p in non-small cell lung cancer

“…miR-30a-5p has received more attention due to its important role in various biological and pathological processes, including development, differentiation, autophage and apoptosis (22,23).…”