Targeted Inhibition Of MiRNA Maturation With Morpholinos Reveals A Role For MiR-375 In Pancreatic Islet Development

Main Category: Genetics
Also Included In: Diabetes;  Endocrinology
Article Date: 24 Jul 2007 - 15:00 PDT

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The striking tissue-specific expression patterns of microRNAs (miRNAs) suggest that they play a role in tissue development. These small RNA molecules (~22 bases in length) are processed from long primary transcripts (pri-miRNA) and regulate gene expression at the posttranscriptional level.

There are hundreds of different miRNAs, many of which are strongly conserved. Vertebrate embryonic development is most easily studied in zebrafish, but genetically disrupting miRNA genes to see which miRNA does what is technically challenging. In this study, the researchers interfere with miRNA function during the first few days of zebrafish embryonic development by introducing specific antisense morpholino oligonucleotides (morpholinos have been used previously to interfere with the synthesis of the much larger mRNAs). They show that morpholinos targeting the miRNA precursor can block processing of the pri-miRNA or directly inhibit the activity of the mature miRNA.

The researchers also used morpholinos to study the developmental effects of miRNA knockdown. Although they did not observe gross phenotypic defects for many miRNAs, they found that zebrafish miR-375 is essential for formation of the insulin-secreting pancreatic islet. Loss of miR-375 results in dispersed islet cells by 36 hours postfertilization, representing one of the first vertebrate miRNA loss-of-function phenotypes.

Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RHA (2007)
Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development.
PLoS Biol 5(8): e203. doi:10.1371/journal.pbio.0050203.
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