Regulation of the Drosophila lin‐41 homologue dappled by let‐7 reveals conservation of a regulatory mechanism within the LIN‐41 subclade

Abstract

Drosophila Dappled (DPLD) is a member of the RBCC/TRIM superfamily, a protein family involved in numerous diverse processes such as developmental timing and asymmetric cell divisions. DPLD belongs to the LIN-41 subclade, several members of which are micro RNA (miRNA) regulated. We re-examined the LIN-41 subclade members and their relation to other RBCC/TRIMs and dpld paralogs, and identified a new Drosophila muscle specific RBCC/TRIM: Another B-Box Affiliate, ABBA. In silico predictions of candidate miRNA regulators of dpld identified let-7 as the strongest candidate. Overexpression of dpld led to abnormal eye development, indicating that strict regulation of dpld mRNA levels is crucial for normal eye development. This phenotype was sensitive to let-7 dosage, suggesting let-7 regulation of dpld in the eye disc. A cell-based assay verified let-7 miRNA down-regulation of dpld expression by means of its 3 -untranslated region. Thus, dpld seems also to be miRNA regulated, suggesting that miRNAs represent an ancient mechanism of LIN-41 regulation. Developmental Dynamics 237:196 -208, 2008.

Abba is an essential TRIM/RBCC protein for maintaining the integrity of sarcomeric cytoarchitecture

“…Abba, belongs to the TRIM/RBCC protein family, whose members are involved in a variety of cellular processes and exhibit characteristic features, which include a RING finger domain, one or two zinc-binding Bboxes and a coiled-coil domain (Meroni and Diez-Roux, 2005;O'Farrell et al, 2008). In some members, NHL repeats are found in the C-terminal region (Slack and Ruvkun, 1998).…”

The role of let-7 in cell differentiation and cancer

“…DAF-12 itself is a target of let-7 at later stages, indicating that feed forward and feedback loops are involved in driving different stage transitions (Grosshans et al 2005). While DAF-12 seems to be a nematode-specific let-7 target, other targets such as RAS (homolog of let-60) and TRIM71 (lin-41) are conserved among various organisms (Kloosterman et al 2004, Schulman et al 2005, Lin et al 2007, Yu et al 2007a, O'Farrell et al 2008.…”

A matter of timing: microRNA-controlled temporal identities in worms and flies

“…For the most part, the predicted targets of Drosophila let-7 differ from those predicted for C. elegans let-7 (Grun et al 2005;Lall et al 2006). However, a recent study showed that a Drosophila lin-41 homolog is a likely target of let-7, a possibility that can now be tested more rigorously with the newly available materials (O'Farrell et al 2008). Sokol et al (2008) cite unpublished observations indicating that abrupt, which encodes a BTB-domain transcription factor, may be a functional let-7 target.…”