Downregulation of the Host Gene jigr1 by miR-92 Is Essential for Neuroblast Self-Renewal in Drosophila.

Yeliz Yuva-Aydemir,Xia-Lian Xu,Ozkan Aydemir,Serkan Sayin,Wenke Zhou,Fen-Biao Gao,Eduardo Gascon,Yang Hong,Bingwei Lu

doi:10.1371/journal.pgen.1005264

Abstract

Intragenic microRNAs (miRNAs), located mostly in the introns of protein-coding genes, are often co-expressed with their host mRNAs. However, their functional interaction in development is largely unknown. Here we show that in Drosophila, miR-92a and miR-92b are embedded in the intron and 3’UTR of jigr1, respectively, and co-expressed with some jigr1 isoforms. miR-92a and miR-92b are highly expressed in neuroblasts of larval brain where Jigr1 expression is low. Genetic deletion of both miR-92a and miR-92b demonstrates an essential cell-autonomous role for these miRNAs in maintaining neuroblast self-renewal through inhibiting premature differentiation. We also show that miR-92a and miR-92b directly target jigr1 in vivo and that some phenotypes due to the absence of these miRNAs are partially rescued by reducing the level of jigr1. These results reveal a novel function of the miR-92 family in Drosophila neuroblasts and provide another example that local negative feedback regulation of host genes by intragenic miRNAs is essential for animal development.

Highlights

MicroRNAs are short (~21–23 nt) noncoding RNAs that regulate gene expression post-transcriptionally in many physiological and pathological processes [1,2]
Animal development is regulated by many genes including a class of small RNAs called microRNAs
We use Drosophila stem cells in the brain as a model system to investigate the interactions between miR-92a and miR-92b and their host gene jing interacting regulatory protein 1

Summary

Introduction

MicroRNAs (miRNAs) are short (~21–23 nt) noncoding RNAs that regulate gene expression post-transcriptionally in many physiological and pathological processes [1,2]. Many intronic miRNAs and host gene mRNAs are likely co-expressed [5,6] but others may not be [7,8]. We used the differentiation of Drosophila neuroblasts as a model system to examine the expression and function of specific miRNAs. Drosophila neuroblasts form during embryonic development and enter a proliferative quiescent state at the end of embryogenesis [9]. In the early larval stage, neuroblasts reenter the cell cycle and undergo a series of proliferative symmetric and self-renewing asymmetric cell divisions to maintain the progenitor pool and generate diverse cell types [10,11]. The balance between self-renewal and differentiation is critical for normal development, but the mechanisms are incompletely understood [12]

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Conclusion